Is the use of gonad protection protectors necessary during infants chest radiography?

INTRODUCTION AND OBJECTIVES: To compare gonad doses with and without a gonad protector and to optimize the use of gonadal protectors in infants thorax radiography. MATERIALS AND METHODS: Two pediatric anthropomorphic phantoms are used: an X-ray system for KXO-50SS/DRX-3724HD, and a digital radiography system for CALNEO Smart C12, with and without a gonad protector during infants thorax radiography. A real time skin dosimeter is placed on the X-ray system, and a real time skin dosimeter is inserted on the front side of the mammary gland, the front and back sides of the true pelvis level, and on the ovaries and testes. The X-ray system is irradiated 15 times using phantoms with and without a gonad protector. The measured entrance patient doses values of for the real time skin dosimeter are compared for each phantom, with and without the gonad protector. RESULTS: The medium of measured entrance patient doses values for front side dose of the true pelvis level with and without the protector are 10.00 and 5.00 µGy at newborn, and 10.00 and 0.00µGy at one year, respectively. The medium of measured entrance patient doses values for the back side dose of the true pelvis level with and without the protector are 0.00 and 0.00 µGy at both newborn one year, respectively. The measured entrance patient doses cannot be detected in the ovaries and testes with or without the protector. No significant differences are observed in the measured entrance patient doses values for the front and back side doses of the pelvis, ovaries, and testes at newborn and one year, with and without the protector (p>0.05). CONCLUSIONS: No significant difference was observed in gonad dose measurements with and without the gonad protector during infants chest radiography. We believe that gonadal protector wearing is not necessary.

¿Es necesario utilizar protectores de gónadas durante la realización de radiografías de tórax en los lactantes? / Is the use of gonad protection protectors necessary during infants chest radiography?

Introducción y objetivos: Comparar las dosis de radiación en las gónadas con y sin protector gonadal y optimizar el uso de estos protectores al realizar radiografías de tórax a lactantes. Materiales y métodos: Se utilizan 2 maniquíes antropomórficos pediátricos, un sistema de rayos X KXO-50SS/DRX-3724HD, y un sistema de radiografía digital CALNEO Smart C12, con y sin protector de gónadas durante la realización de radiografías de tórax. Se coloca un dosímetro cutáneo en tiempo real en el sistema de rayos X y se inserta un dosímetro cutáneo en tiempo real en la cara anterior de la glándula mamaria, en la cara anterior y posterior de la pelvis verdadera, y en los ovarios y testículos. El sistema de rayos X se irradia 15 veces con maniquíes, con y sin el protector de gónadas. Se comparan los valores de las dosis de entrada del paciente medidos por el dosímetro cutáneo en tiempo real para cada maniquí, con y sin el protector de gónadas. Resultados: Los valores medios de las dosis a la entrada del paciente medidos para la cara anterior a nivel de la pelvis verdadera, con y sin el protector, son 10,00 y 5,00μGy en el recién nacido, y 10,00 y 0,00μGy al año, respectivamente. Los valores medios de las dosis a la entrada del paciente medidos para la cara posterior a nivel de la pelvis verdadera con y sin el protector son de 0,00 y 0,00μGy tanto en el recién nacido como al año, respectivamente. Las dosis a la entrada del paciente medidas no se pueden detectar en los ovarios y los testículos ni con el protector ni sin él. No se observan diferencias significativas en los valores de las dosis a la entrada del paciente medidas en la cara anterior y posterior de la pelvis, los ovarios y los testículos en el recién nacido y al año, con y sin el protector (p>0,05).(AU)

Introduction and objectives: To compare gonad doses with and without a gonad protector and to optimize the use of gonadal protectors in infants thorax radiography. Materials and methods: Two pediatric anthropomorphic phantoms are used: an X-ray system for KXO-50SS/DRX-3724HD, and a digital radiography system for CALNEO Smart C12, with and without a gonad protector during infants thorax radiography. A real time skin dosimeter is placed on the X-ray system, and a real time skin dosimeter is inserted on the front side of the mammary gland, the front and back sides of the true pelvis level, and on the ovaries and testes. The X-ray system is irradiated 15 times using phantoms with and without a gonad protector. The measured entrance patient doses values of for the real time skin dosimeter are compared for each phantom, with and without the gonad protector. Results: The medium of measured entrance patient doses values for front side dose of the true pelvis level with and without the protector are 10.00 and 5.00μGy at newborn, and 10.00 and 0.00μGy at one year, respectively. The medium of measured entrance patient doses values for the back side dose of the true pelvis level with and without the protector are 0.00 and 0.00μGy at both newborn one year, respectively. The measured entrance patient doses cannot be detected in the ovaries and testes with or without the protector. No significant differences are observed in the measured entrance patient doses values for the front and back side doses of the pelvis, ovaries, and testes at newborn and one year, with and without the protector (p>0.05). Conclusions: No significant difference was observed in gonad dose measurements with and without the gonad protector during infants chest radiography. We believe that gonadal protector wearing is not necessary.(AU)

Influence of contrast enhancement at the contrast injection location for the arm or leg in neonatal and infant patients during cardiac computed tomography.

INTRODUCTION AND OBJECTIVES: Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients. PATIENTS OR MATERIALS AND METHODS: Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n = 58) and leg (n = 58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast-noise ratios (CNR); and visualization scores between the arm and leg as the injection locations. RESULTS: The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations. CONCLUSIONS: The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.

Influencia del realce de contraste al inyectar un medio de contraste en el brazo o la pierna en pacientes neonatos y lactantes durante la angiografía por cardiotomografía / Influence of Contrast Enhancement at the Contrast Injection Location for the Arm or Leg in Neonatal and Infant Patients during Cardiac Computed Tomography

Introducción y objetivos: En la obtención de imágenes de angiografía por cardiotomografía (ACT) es importante escoger una ubicación adecuada para inyectar el medio de contraste (p. ej., el brazo o la pierna) a fin de evitar la formación de artefactos que este provoca. En este estudio se comparan los valores de tomografía computarizada (TC) y las puntuaciones de visualización de las imágenes tridimensionales (3D) de los lúmenes de los vasos sanguíneos del brazo y la pierna durante la ACT en pacientes neonatos y lactantes. Pacientes o materiales y métodos: Entre los meses de enero de 2017 y enero de 2020 se evaluaron 253 pacientes de forma consecutiva para determinar su inclusión en el estudio. Se utilizaron las puntuaciones de propensión estimadas en función de los datos demográficos, incluidos la edad, el peso corporal y la ubicación de la inyección (lado derecho o izquierdo) en el brazo (n=58) y la pierna (n=58) de los pacientes neonatos y lactantes. A continuación, se compararon los valores medios de TC de la arteria pulmonar, la aorta ascendente y la vena cava superior izquierda; las relaciones contraste-ruido (RCR); y las puntuaciones de visualización del brazo y la pierna como lugares de inyección. Resultados: Los valores medios de TC durante la ACT para el brazo y la pierna fueron de 479,4 y 461,3 UH en la aorta ascendente, de 464,2 y 448,1 UH en la arteria pulmonar y de 232,8 y 220,1 UH en la vena cava superior izquierda, respectivamente. Los valores medios de ruido de la imagen (DE) y de RCR fueron, respectivamente, de 38,9 y 12,1 UH para el brazo y de 39,1 y 12,3 UH para la pierna. Las puntuaciones medias de visualización de la representación del volumen de las imágenes 3D fueron de 3,0 y 3,0 para los lugares de inyección del brazo y la pierna, respectivamente.(AU)

Introduction and Objectives: Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients. Patients or Materials and Methods: Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n=58) and leg (n=58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast–noise ratios (CNR); and visualization scores between the arm and leg as the injection locations. Results: The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations. Conclusions: The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.(AU)

Applying patient characteristics, stent-graft selection, and pre-operative computed tomographic angiography data to a machine learning algorithm: Is endoleak prediction possible?

INTRODUCTION: This study aims to predict endoleak after endovascular aneurysm repair (EVAR) using machine learning (ML) integration of patient characteristics, stent-graft configuration, and a selection of vessel lengths, diameters and angles measured using pre-operative computed tomography angiography (CTA). METHODS: We evaluated 1-year follow-up CT scans (arterial and delayed phases) in patients who underwent EVAR for the presence or absence of an endoleak. We also obtained data on the patient characteristics, stent-graft selection, and preoperative CT vessel morphology (diameter, length, and angle). The extreme gradient boosting (XGBoost) for the ML system was trained on 30 patients with endoleaks and 81 patients without. We evaluated 5217 items in 111 patients with abdominal aortic aneurysms, including the patient characteristics, stent-graft configuration and vascular morphology acquired using pre-EVAR abdominal CTA. We calculated the area under the curve (AUC) of our receiver operating characteristic analysis using the ML method. RESULTS: The AUC, accuracy, 95% confidence interval (CI), sensitivity, and specificity were 0.88, 0.88, 0.79-0.97, 0.85, and 0.91 for ML applying XGBoost, respectively. CONCLUSIONS: The diagnostic performance of the ML method was useful when factors such as the patient characteristics, stent-graft configuration and vessel length, diameter and angle of the vessels were considered from pre-EVAR CTA. IMPLICATIONS FOR PRACTICE: Based on our findings, we suggest that this is a potential application of ML for the interpretation of abdominal CTA scans in patients with abdominal aortic aneurysms scheduled for EVAR.

Formulation of energy loss in a four-way circular manhole at crossroad.

Energy loss at a manhole which is at a junction of storm sewers or combined sewers is important for accurately estimating its discharge capacity. However, even in Japan, the energy loss at the manhole is usually ignored in designing sewers and flood inundation analysis. One of the reasons for the ignorance is difficulty to formulate the energy loss at the manhole because the number of variables which must be considered increases as the number of sewers connected to the manhole increases. The authors have formulated the energy loss of a four-way circular manhole with three inflow sewers and one outflow sewer at crossroad. The formula is applicable only to the equal flow rates in two opposite lateral inflow sewers. In this paper, a new formula for the energy losses is proposed based on experimental data on a four-way circular manhole with different flow rates on three inflow sewers. It shows that the energy losses calculated with it almost reproduce the measured ones.

Radiation dose reduction method combining the ECG-Edit function and high helical pitch in retrospectively-gated CT angiography.

INTRODUCTION: The purpose of this study was to demonstrate that dose reduction does not compromise image quality when combining high helical pitch (HP) and the ECG-Edit function during low HP retrospectively gated computed tomography angiography (CTA). METHODS: This study made use of a pulsating cardiac phantom (ALPHA 1 VTPC). The heart rate (HR) of the cardiac phantom was changed in five intervals, every 5 beats per minute (bpm), from 40 to 60 bpm. Evaluation of a range of HR was important because data loss might occur when combining a low HR and high HP. We performed retrospectively gated CTA scans five times using a low HP (0.16) and high HP (0.24), for each of the five HR intervals, using a 64-detector row CT scanner. The CT volume dose index (CTDIvol) was recorded from the CT console of each scan. For the images with data loss, data were repaired using the ECG-Edit function. We compared the CTDIvol, estimated cardiac phantom volume, and the visualization of the coronary ladder phantom between HP 0.16, with or without repaired HP 0.24, using the ECG-Edit function. RESULTS: Data loss occurred with a HR of 40 bpm and 45 bpm when using HP 0.24. The CTDIvol was reduced by approximately 33% with HP 0.24 when compared with HP 0.16. There were no significant differences in the mean cardiac motion phantom volume and visualization scores between HP 0.16 and with and without repaired HP 0.24 using the ECG-Edit function (p < 0.05). CONCLUSION: The ECG-Edit function is potential useful for repairing the lost data in patients with a low HR, and when combined with a high HP, it is possible to reduce the radiation dose by approximately 33%. IMPLICATIONS FOR PRACTICE: The ECG-Edit function and high HP may be a viable option in pediatric CTA studies.

Effect of injection duration on contrast enhancement during cardiac computed tomography angiography in newborns and infants.

INTRODUCTION: To investigate how changing the injection duration at cardiac computed tomography angiography (CCTA) affects contrast enhancement in newborns and infants. METHODS: Included were 142 newborns and infants with confirmed congenital heart disease who underwent CCTA between January 2015 and December 2018. In group 1 (n = 71 patients), the injection duration was 8 s; in group 2 (n = 71) it was 16 s. Our findings were assessed by one-to-one matching analysis to estimate the propensity score of each patient. We compare the CT number for the pulmonary artery (PA), ascending aorta (AAO), left superior vena cava (SVC), AAO and PA enhancement ratio, and the scores for visualization between the two groups. RESULTS: In group 1, median CT number and ranges was 345 (211-591) HU in the AAO, 324 (213-567) HU in the PA, and 62 (1-70) HU in the SVC. These values were 465 (308-669) HU, 467 (295-638) HU, and 234 (67-443) HU, respectively, in group 2 (p < 0.05). The median score for volume-rendering visualization on 3D images of the CCTA was 2 in group 1 and 3 in group 2; the score for visualization of the left SVC of the maximum intensity projection images was 2 in group 1 and 3 in group 2 (p < 0.05). The CT number for the AAO and PA enhancement ratio was 15.2 in group 1 and 9.2 in group 2 (p < 0.05). CONCLUSION: The 16-sec injection protocol yielded significantly higher CT numbers for the AAO, PA, and the SVC than the 8-sec injection protocol; the visualization scores were also significantly higher in group 2. IMPLICATIONS FOR PRACTICE: In newborns and infants, the longer injection time for CCTA yields stable and higher contrast enhancement at identical CM concentrations.

Deep learning with convolutional neural network for estimation of the characterisation of coronary plaques: Validation using IB-IVUS.

INTRODUCTION: Deep learning approaches have shown high diagnostic performance in image classifications, such as differentiation of malignant tumors and calcified coronary plaque. However, it is unknown whether deep learning is useful for characterizing coronary plaques without the presence of calcification using coronary computed tomography angiography (CCTA). The purpose of this study was to compare the diagnostic performance of deep learning with a convolutional neural network (CNN) with that of radiologists in the estimation of coronary plaques. METHODS: We retrospectively enrolled 178 patients (191 coronary plaques) who had undergone CCTA and integrated backscatter intravascular ultrasonography (IB-IVUS) studies. IB-IVUS diagnosed 81 fibrous and 110 fatty or fibro-fatty plaques. We manually captured vascular short-axis images of the coronary plaques as Portable Network Graphics (PNG) images (150 × 150 pixels). The display window level and width were 100 and 700 Hounsfield units (HU), respectively. The deep-learning system (CNN; GoogleNet Inception v3) was trained on 153 plaques; its performance was tested on 38 plaques. The area under the curve (AUC) obtained by receiver operating characteristic analysis of the deep learning system and by two board-certified radiologists was compared. RESULTS: With the CNN, the AUC and the 95% confidence interval were 0.83 and 0.69-0.96, respectively; for radiologist 1 they were 0.61 and 0.42-0.80; for radiologist 2 they were 0.68 and 0.51-0.86, respectively. The AUC for CNN was significantly higher than for radiologists 1 (p = 0.04); for radiologist 2 it was not significantly different (p = 0.22). CONCLUSION: DL-CNN performed comparably to radiologists for discrimination between fatty and fibro-fatty plaque on CCTA images. IMPLICATIONS FOR PRACTICE: The diagnostic performance of the CNN and of two radiologists in the assessment of 191 ROIs on CT images of coronary plaques whose type corresponded with their IB-IVUS characterization was comparable.

Efficacy of the spiral flow generating extended tube during paediatric CCTA.

INTRODUCTION: To compare the computed tomography (CT) number for paediatric cardiac computed tomography angiography (CCTA) and visualisation score of the three-dimensional (3D) images using the conventional T-shaped extended tube (T-tube) and spiral flow-generating extended tube (spiral-tube) connected between the contrast injector and cannula. METHODS: In total, 108 patients suspected to have congenital heart disease (CHD) were considered for inclusion. We utilised the T-tube for intravenous contrast and spiral-tube in 54 patients each. Observers individually inspected randomized volume rendering images of the internal thoracic artery, each acquired from the with or without spiral-tube groups, using a four-point scale. We compared the mean CT number of the ascending aorta (AAO) and pulmonary artery (PA), contrast noise ratio (CNR), CT number for the AAO and PA enhancement ratio, and the visualisation scores between the groups. RESULTS: There were no significant differences in patient characteristics between the with or without spiral-tube groups (p > 0.05). The mean CT number ±standard deviation for the AAO and PA, and the CNR without or with spiral-tube groups were 441.2 ± 89.2 and 489.8 ± 86.1 HU for the AAO, 436.3 ± 100.6 and 475.3 ± 85.2 HU for the PA, and 9.5 ± 2.2 and 10.8 ± 2.4 for the CNR, respectively (p < 0.05). In the spiral-tube group, the CT number, CNR, and visualisations score of the 3D images were significantly higher for the AAO and PA than those in the T-tube group (p < 0.05). CONCLUSION: The spiral-tube proved to be beneficial in improving the CT number for the AAO and PA, CNR, and visualisation score compared with the conventional T-tube during paediatric CCTA. IMPLICATIONS FOR PRACTICE: The spiral-tube may allow the visualisation of smaller blood vessels than those visualised by the conventional T-tube for paediatric patients in CCTA.

Enhancement rate of venous phase to portal venous phase computed tomography and its correlation with ultrasound elastography determination of liver fibrosis.

INTRODUCTION: This study aimed to compare the correlation between the computed tomography (CT) enhancement rate of the venous to portal venous phase (VP-ER) and the extracellular volume (ECV) fraction with shear-wave ultrasound elastography (USE) findings in patients with liver fibrosis. METHODS: We included 450 patients with clinically suspected liver cirrhosis who underwent triphasic dynamic CT studies and USE. We compared the USE results with the unenhanced CT phase, with enhancement in the hepatic artery phase (HAP), portal venous phase (PVP), and venous phase (VP), and with the ECV fraction and the VP-ER. We also compared the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the ECV fraction and VP-ER with that of the values obtained with USE. RESULTS: The VP-ER was the most highly correlated with the liver stiffness value determined with USE (Pearson's correlation coefficient: r = 0.37), followed by enhancement in the PVP (r = -0.25), CT number on unenhanced CT scans (r = -0.22), the ECV fraction (r = 0.19), enhancement in the VP (r = 0.059), and enhancement in the HAP (r = -0.023) (all p < 0.01). The VP-ER showed a significantly higher AUC than the ECV fraction (0.75 vs 0.62) when the liver stiffness was >15 kPa in USE studies (p = 0.04). CONCLUSION: Compared to the ECV fraction, the VP-ER is more useful for predicting all degrees of liver fibrosis on routine triphasic dynamic CT images. IMPLICATIONS FOR PRACTICE: Although improvement is needed, the VP-ER has a higher diagnostic ability for liver fibrosis than the ECV fraction in clinical practice.

Fas antigen expression on hepatocytes predicts the short- and long-term response to interferon therapy in patients with chronic hepatitis C.

BACKGROUND: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV) -induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short-and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. METHODS: Ten million units of recombinant IFN-alpha2b were administered daily for the first 2 weeks, and three times a week for another 22 weeks. The short-term efficacy of IFN therapy was evaluated after 12-month follow-up from cessation of treatment. We also examined the long-term response to IFN at 56.6 +/- 10.8 (mean +/- s) months after termination of IFN therapy in 55 of 72 patients. RESULTS: Univariate analysis showed that serum HCV-RNA levels, HCV genotype and Fas expression significantly correlated with the short-term efficacy of IFN therapy (P = 0.005, 0.006, and 0.04, respectively). Fas antigen expression did not correlate with serum HCV-RNA levels (P = 0.286), but significantly correlated with HCV genotype (P = 0.003). Multivariate analysis indicated that Fas expression and serum HCV-RNA levels were independent determinants of the short-term response to IFN therapy. Combined together, Fas expression and serum HCV-RNA levels accurately predicted the short-term response to IFN therapy. On the other hand, in 55 patients who were examined the long-term response to IFN, about 60% of Fas-positive patients were HCV-RNA negative, whereas 30% of Fas-negative patients were HCV-RNA negative (P = 0.04). Among Fas-positive patients, the percentage of those with serum ALT levels persistently lower than twice the normal upper limit in long-term study (81.8%; 9/11) was significantly higher than those in short-term study even among patients who failed to show elimination of HCV-RNA (36.4%; 4/11, P = 0.03). CONCLUSION: Our results indicate that Fas expression on hepatocytes is a good predictor of the short-and long-term response to IFN therapy.

Beta1 integrins play an essential role in adhesion and invasion of pancreatic carcinoma cells.

To investigate the role of beta1 integrins in pancreatic carcinoma invasion, we analyzed the relationship between the activity of beta1 integrins and the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxPC3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of beta1 and alpha6 subunits, and various levels of alpha2, alpha3, and alpha5 expression as determined by flow cytometry. Cell adhesion assay revealed that alpha2beta1, alpha5beta1, and alpha6beta1 integrins were the predominant adhesion receptors for collagen, fibronectin, and laminin, respectively. Beta1 integrins on different cell types showed a wide range of constitutive activity. Anti-beta1 monoclonal antibody (MAB) TS2/16 rapidly activated beta1 integrins, and thus TS2/16 requirement in cell adhesion represented the levels of constitutive activity of beta1 integrins. Notably, as the result of in vitro chemoinvasion assay, the levels of constitutive activity of beta1 integrins correlated with the invasive ability of pancreatic carcinoma cells. The inhibitory anti-beta1 MAB 13 completely blocked the invasion of these cell lines. Alternatively, the stimulatory anti-beta1 MAB TS2/16 strongly inhibited the invasion. These results show an essential role of beta1 integrins in invasion of pancreatic carcinoma cells and also suggest subtle regulatory mechanisms of cell invasion.

Expression of the thymidine phosphorylase gene in epithelial ovarian cancer.

Thymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumours. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear cell and two undifferentiated) were analysed by polymerase chain reaction of RNA after reverse transcription. These included eight of low malignant potential. Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the beta2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III-IV was significantly higher than that of TP gene expression in stage I-II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases after complete resection of the primary tumours by surgical operation was performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to, or greater than, median) was to be significantly worse than patients with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumour phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated.

Measurement of urinary lactoferrin as a marker of urinary tract infection.

The usefulness of the measurement of urinary lactoferrin (LF) released from polymorphonuclear leukocytes and of an immunochromatography test strip devised for measuring urinary LF for the simple and rapid diagnosis of urinary tract infections (UTI) was evaluated. Urine specimens were collected from apparently healthy persons and patients diagnosed as suffering from UTI. In the preliminary study, the LF concentrations in 121 normal specimens and 88 specimens from patients (60 with UTI) were quantified by an enzyme-linked immunosorbent assay. The LF concentration was 3,300.0 +/- 646.3 ng/ml (average +/- standard error of the mean) in the specimens from UTI patients, whereas it was 30.4 +/- 2.7 ng/ml and 60.3 +/- 14.9 ng/ml in the specimens from healthy persons and the patients without UTI, respectively. Based on these results, a 200-ng/ml LF concentration was chosen as the cutoff value for negativity. Each urine specimen was reexamined with the newly devised immunochromatography (IC) test strip to calculate the indices of efficacy. Based on the cutoff value, it was calculated that the sensitivity, specificity, and positive and negative predictive values of the IC test were 93.3, 89.3, 86.2, and 94.9%, respectively, compared with the results of the microscopic examination of the urine specimens for the presence of leukocytes. The respective indices for UTI were calculated as 95.0, 92.9, 89.7, and 96.6%. The tests were completed within 10 min. These results indicated that urine LF measurement with the IC test strip provides a useful tool for the simple and rapid diagnosis of UTI.

Role of beta1 integrins in adhesion and invasion of hepatocellular carcinoma cells.

To investigate the role of integrins in hepatocellular carcinoma (HCC) invasion, we analyzed the relationship between the expression and activity of beta1 integrins and the invasive ability of multiple HCC cell lines. Human HCC cell lines, PLC/PRF/5, Hep3B, HepG2, HLE, HuH7, and C3A cells, had high expression of beta1 and alpha6 subunits, and various levels of alpha1, alpha2, alpha3, and alpha5 expression as determined by cell surface flow cytometry. Activity of beta1 integrins was evaluated by cell adhesion to collagen, fibronectin, and laminin in the presence or absence of the stimulatory anti-beta1 monoclonal antibody (mAb) TS2/16. Different types of HCC cells showed various levels of constitutive activity of beta1 integrins as assessed by the TS2/16 requirement in cell adhesion. TS2/16 rapidly stimulated constitutively inactive or partially active beta1 integrins to fully active states, and as the result, the levels of cell adhesion to each ligand correlated with the expression levels of corresponding beta1 integrins. Thus, in the presence of TS2/16 stimulation, the levels of cell adhesion to collagen, fibronectin, and laminin correlated predominantly with the expression levels of alpha2, alpha5, and alpha6, respectively. Remarkably, as a result of in vitro chemoinvasion assay, the levels of constitutive activity of beta1 integrins correlated with the invasive ability of HCC cells. The inhibitory anti-beta1 mAb 13 almost completely blocked the invasion of PLC/PRF/5 and Hep3B cells that are the most invasive HCC cell lines. Alternatively, the stimulatory anti-beta1 mAb TS2/16 strongly inhibited the invasion. These results not only show an essential role of beta1 integrins in invasion of HCC cells but also suggest subtle regulatory mechanisms of cell invasion.

Expression patterns of multidrug-resistance (MDR1), multidrug resistance-associated protein (MRP),glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in renal cell carcinomas and normal kidney.

PURPOSE: Expression levels of the multidrug-resistance (mdr1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in normal kidney and renal cell carcinomas were analyzed to study the complexity of the roles of these genes. MATERIALS AND METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) assay was used with beta 2 microglobulin (beta 2 m) as the internal control. RESULTS: In normal kidneys, the expression levels of the 4 genes in individual normal kidney samples correlated significantly with one another. Comparisons of the expression levels between normal kidneys and renal cell carcinomas showed that only the mean MRP gene expression level was higher in renal cell carcinomas than in normal kidneys (p = 0.018). The expression patterns of the 4 genes in renal cell carcinomas differed markedly for nonpapillary and papillary tumors. The mean MRP/beta 2 m ratio for the papillary type was significantly lower than that for the nonpapillary alveolar type carcinoma (p = 0.004). The 4 genes showed moderate positive correlations with one another in alveolar type renal carcinoma similar to the correlations observed in normal kidneys. In contrast, in papillary type, MRP expression was inversely correlated with mdr1 and Topo II expression. CONCLUSION: Differences in cytogenetic changes, origins and natural histories between papillary and nonpapillary carcinoma may be associated with these distinct expression patterns of the resistance-related genes. Further study is required to clarify whether the differences in the expression patterns between these 2 structural types of carcinoma affect their chemosensitivities and clinical outcomes.

Immunohistochemical localization of P-glycoprotein and expression of the multidrug resistance-1 gene in human pancreatic cancer: relevance to indicator of better prognosis.

We investigated immunohistochemical localization of P-glycoprotein (P-gp) on paraffin-embedded sections from 103 cases of previously untreated pancreatic tumors and also analyzed multidrug resistance-1 (MDR1) gene expression by polymerase chain reaction after reverse transcription in 35 cases. High positive staining for P-gp was observed in 72.8% of pancreatic tumors and in 73.2% of ductal adenocarcinoma. In ductal adenocarcinoma, immunoreactivity of P-gp was inversely correlated with biological aggressiveness of tumors determined by histologic grading (P<0.01), tumor size (P < 0.01), retroperitoneal invasion (P < 0.01) and portal invasion (P < 0.05). Expression of the MDR1 gene was detected in all the pancreatic tumors examined and was significantly higher than that in normal pancreas (P < 0.05). The levels of MDR1 mRNA showed a moderate correlation with those of P-gp (r=0.62, P<0.0001). Higher expression levels of MDR1/P-gp significantly correlated with better prognosis of patients with ductal carcinoma (P < 0.05). Among patients with ductal carcinoma, the high staining group for P-gp revealed a 3.5-fold better prognosis compared with the low staining group (HR=3.47, 95% CI=1.62, 7.45; P=0.0016). In conclusion, MDR1 gene/P-gp expression in pancreatic cancer without chemotherapy inversely correlates with biological aggressiveness and is an independent indicator of favorable prognosis.