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PubMed2005

Ultrasound-detected thyroid nodules in radiation-exposed patients: changes over time.

The relationship between radiation exposure and thyroid cancer is well known, but whether all irradiated patients should have thyroid ultrasounds is unresolved. We have performed follow-up ultrasound examinations of patients in a cohort who were exposed to conventional external radiation during 1939-63 for benign conditions of the head and neck area prior to their 16th birthday. Of 54 subjects who had normal radionuclide scans in 1974-76 and were reexamined in 1996-97 by thyroid ultrasonography, 42 remained eligible and 34 agreed to participate in the present ultrasound study. After an additional 4-8 years of follow-up and using an ultrasound machine with increased resolution, we found 160 nodules (in 33 of these 34 subjects), compared with 96 nodules (in 29 of the 34 subjects) detected in the previous examination. Only four of the new nodules were > or =10 mm. Of the previously diagnosed large (> or =10 mm) nodules, four nodules in four subjects resolved; nine nodules in six subjects regressed to <10 mm; 14 nodules in 13 subjects remained at > or =10 mm. The four new large nodules appeared in four subjects, and six small nodules increased to > or =10 mm in six other subjects. The total volume of the thyroid nodules decreased in the 13 subjects on thyroid hormone (by 0.20 cm(3)) and increased in the 21 subjects who were not (by 0.34 cm(3), p < 0.05 by unpaired t-test). In summary, thyroid nodules are extremely common in irradiated subjects. Many new ones may be observed over time, but most are small and seen because of the increased resolution of ultrasound machines. Compared to patients on no medication, nodules in patients on thyroid hormone tended to regress. Since FNA of all thyroid nodules in irradiated patients is not feasible, ultrasound is useful in identifying those lesions that are growing.

Female↗

PubMed2000

The role of 99Tcm-tetrofosmin in the evaluation of thyroid nodules.

Various radionuclides, including 67Ga, 201Tl and 99Tcm-sestamibi, have been used to differentiate benign from malignant thyroid nodules. 99Tcm-tetrofosmin, a lipophilic cationic radiotracer, and 99Tcm-sestamibi have also been reported to accumulate in thyroid tumours. In this study, we evaluated the role of 99Tcm-tetrofosmin in the differentiation of malignant from benign thyroid nodules. Seventy-nine patients with solitary non-functioning thyroid nodules were included in the study. Fine-needle aspiration biopsy was performed in all patients. Sixty patients were subsequently operated on and 19 patients refused surgery. After the injection of 370 MBq 99Tcm-tetrofosmin, static images at 5, 30, 60, 120 and 180 min were acquired. Both visual and semi-quantitative analysis was performed. On visual interpretation, the nodules with late retention were classified as positive for malignancy and nodules without late retention were classified as negative for malignancy. In the semi-quantitative analysis, regions of interests were drawn over the nodule and contralateral normal thyroid tissue. The average number of counts was recorded and tumour-to-normal thyroid tissue ratios calculated. Post-operative histology revealed 19 malignant and 41 benign nodules. Of the benign nodules, adenomas behaved similarly to the malignant nodules with late retention of tracer, while adenomatous nodules revealed no late retention on delayed images and could be differentiated from malignant tumours. In the semi-quantitative analysis, there was a significant difference in tumour-to-normal tissue ratios for adenomatous nodules and malignant tumours as well as adenomas. We conclude that it is not possible to differentiate between malignant and benign thyroid nodules with 99Tcm-tetrofosmin. However, 99Tcm-tetrofosmin scintigraphy is helpful in selecting nodules that can be cured by surgical intervention.

Adenoma↗

PubMed2004

Solitary pulmonary nodules: dynamic enhanced multi-detector row CT study and comparison with vascular endothelial growth factor and microvessel density.

PURPOSE: To evaluate enhancement dynamics of solitary pulmonary nodules at multi-detector row computed tomography (CT) and to correlate results with extent of tumor angiogenesis in pathologic specimens. MATERIALS AND METHODS: One hundred thirty-one patients with solitary pulmonary nodules underwent unenhanced thin-section CT, followed by dynamic helical CT (throughout the nodule for 30 mm along the z-axis [13 images] and at 20-second intervals for 3 minutes [130 images total]) after intravenous injection of 120 mL of contrast medium. Diagnosis of malignancy or benignancy was assigned in 109 patients, and follow-up imaging suggested benignancy in the remaining 22. CT findings were analyzed for peak attenuation, net enhancement, and enhancement dynamics. In 54 patients with surgical diagnoses, Pearson correlation coefficient was used to correlate enhancement pattern with extent of microvessel density and vascular endothelial growth factor (VEGF) staining. RESULTS: With 30 HU or more of net enhancement as a cutoff value in differentiation of malignant and benign nodules, sensitivity for malignant nodules was 99% (69 of 70 malignant nodules), specificity was 54% (33 of 61 benign nodules), positive predictive value was 71% (69 of 97 malignant readings), negative predictive value was 97% (33 of 34 benign readings), and accuracy was 78% (102 of 131 nodules). Peak attenuation was correlated positively with extent of microvessel density (r = 0.369, P =.006) and VEGF staining (r = 0.277, P =.042). Malignant nodules showed significantly higher VEGF expression (P =.009) than that of benign nodules. CONCLUSION: Dynamic enhancement with multi-detector row CT shows high sensitivity and negative predictive values for diagnosis of malignant nodules but low specificity because of highly enhancing benign nodules. Extent of enhancement reflects underlying nodule angiogenesis.

Adult↗

PubMed2005

Solitary pulmonary nodule: characterization with combined wash-in and washout features at dynamic multi-detector row CT.

PURPOSE: To prospectively assess the accuracy of combined wash-in and washout characteristics at dynamic contrast material-enhanced multi-detector row computed tomography (CT) in distinguishing benign from malignant solitary pulmonary nodules. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. The study included 107 patients (62 men, 45 women; mean age, 55 years; range, 22-81 years) with a solitary pulmonary nodule. After unenhanced CT (2.5-mm collimation) scans were obtained, dynamic CT was performed by using a helical technique (series of images obtained throughout the nodule, with 2.5-mm collimation, at 30, 60, 90, and 120 seconds and 4, 5, 9, 12, and 15 minutes) after intravenous injection of contrast medium (120 mL). Tissue diagnosis was made in 70 nodules, and follow-up images showed benignancy in the remaining 37 (no change in size, n = 32; decrease in size, n = 5). CT findings were analyzed in terms of wash-in and washout of contrast medium. Sensitivity, specificity, and accuracy for malignant nodules were calculated by considering both the wash-in and washout characteristics at dynamic CT. RESULTS: There were 49 malignant and 58 benign nodules. When diagnostic criteria for malignancy of both wash-in of 25 HU or greater and washout of 5-31 HU were applied, sensitivity, specificity, and accuracy for malignancy were 94% (46 of 49 nodules), 90% (52 of 58 nodules), and 92% (98 of 107 nodules), respectively. Of 58 benign nodules, 27 showed less than 25 HU wash-in, 14 showed persistent contrast enhancement without washout and with wash-in of 25 HU or greater, and 11 showed washout greater than 31 HU and wash-in of 25 HU or greater. CONCLUSION: Evaluation of solitary pulmonary nodules by analyzing combined wash-in and washout characteristics at dynamic contrast-enhanced multi-detector row CT showed 92% accuracy for distinguishing benign nodules from malignant nodules.

Adult↗

PubMed1998

Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.

Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.

Adenoma↗

PubMed1988

CT densitometry of pulmonary nodules in a frozen human thorax.

The influence of (1) calcium concentration, (2) exposure technique, (3) reconstruction algorithm, (4) nodule size, and (5) nodule location on the CT attenuation values (CT density) of pulmonary nodules was examined in a frozen human thorax. Nodules with calcium concentrations of 0-310 mg/ml and diameters of either 0.95 or 1.59 cm were inserted into a frozen, unembalmed human thorax. The nodules were placed either at the lung apex or 4 cm below the tracheal carina. Each nodule was scanned on a GE CT 9800 scanner; five different exposure techniques were used. The slice thickness was uniformly 1.5 mm. As expected, increasing the kilovoltage caused a significant decrease in CT nodule density in all nodules with calcium concentrations greater than 80 mg/ml. The inverse relationship between kilovoltage and nodule density was exaggerated with increasing calcium concentration. A high-resolution (bone) algorithm gave a significantly higher CT number than did a smoothed (standard) algorithm, regardless of nodule size and location, but this difference could be attributed almost entirely to the edge-enhancement effect of the bone algorithm. The CT density of the larger nodules was significantly higher than that of the smaller nodules at calcium concentrations greater than 65 mg/ml for both standard and bone algorithms. Densities were significantly higher in the mid lung than in the apex with a standard algorithm, but this was not the case with a bone algorithm. The GE CT 9800 scanner had a linear response between CT density and increasing calcium concentration within the confines of a human thorax. A high-resolution (bone) reconstruction algorithm has higher spatial resolution but does show an edge-enhancing effect not found with the smoothed algorithm. Two major variables in CT densitometry for pulmonary nodules are the kilo electron voltage of the X-ray beam and the reconstruction algorithm used; these two parameters should be standardized, with a high kilovoltage and high-resolution algorithm favored on the GE CT 9800 scanner.

Absorptiometry, Photon↗

PubMed1994

Localization of pulmonary nodules before thoracoscopic surgery: value of percutaneous staining with methylene blue.

OBJECTIVE: Video-assisted thoracic surgery (VATS) is a new procedure that makes it possible to see the intrathoracic organs and to resect pulmonary nodules without thoracotomy. Preoperative localization of small nodules that may not be visible or palpable during VATS is desirable. Percutaneous placement of spring hookwires is widely used to localize pulmonary nodules before VATS; infrequently, the adjacent lung parenchyma is also stained with methylene blue. The purpose of this study was to evaluate the effectiveness of methylene blue staining of pulmonary nodules without placement of a hookwire. SUBJECTS AND METHODS: Fifteen pulmonary nodules in 15 patients were localized preoperatively under CT guidance by using techniques identical to those for CT-guided fine-needle aspiration of pulmonary nodules. Approximately 0.3 ml of methylene blue dye was injected into the nodule with a 22-gauge Chiba needle to stain the nodule, the needle pathway, and the visceral pleura. In two patients, a hookwire also was placed. All patients had solitary nodules in which transbronchial or transthoracic biopsy had been unsuccessful. The mean nodule diameter was 16 mm (range, 8-33 mm), and the mean distance to the nearest pleural surface was 10 mm (range, 0-21 mm). The localization procedure required a mean of 32 min (range, 18-47 min). RESULTS: All 15 nodules were stained successfully either in the center or within the margins; the two hookwires were found to be displaced. In three cases, pulmonary hemorrhage occurred as a complication of the percutaneous staining procedure: in one case, subsequent conversion to thoracotomy was necessary owing to pulmonary hemorrhage and additional pleural bleeding during VATS, which resulted from puncture with a trocar directly into the pleural adhesions. Anticipated complications, such as pneumothorax, occurred in five patients; one patient had pleuritic pain, but none required treatment. In one patient, conversion to thoracotomy was done so that an adenocarcinoma could be treated by means of a lobectomy. In two others, thoracotomy was done because of problems with technical devices. CONCLUSIONS: Percutaneous staining of pulmonary nodules is an accurate technique for localizing nodules before VATS. The procedure is easily and safely performed, and it obviates wire-related complications, such as severe pleuritic pain.

Female↗

PubMed2003

The enhancing rim: a new sign of a benign pulmonary nodule.

OBJECTIVE: To describe a new radiological sign, the enhancing rim sign, that indicates that a solitary pulmonary nodule is benign rather than malignant. PATIENTS AND METHODS: Sixteen adult patients underwent computed tomographic (CT) evaluation with intravenous contrast enhancement of an indeterminate solitary pulmonary nodule between May 25, 2000, and March 21, 2002, at the Mayo Clinic in Scottsdale, Ariz. In each patient, we identified a rim of enhancing soft tissue at the periphery of a solitary pulmonary nodule; this rim surrounds a homogeneous, lower-density central portion of the nodule. Surgical or biopsy specimens from 6 patients and clinical data from 10 patients were evaluated to determine whether the nodules with the enhancing rims were benign or malignant. RESULTS: Pulmonary nodules in 6 patients were diagnosed as benign after histological evaluations of tissue obtained by surgical resection (3 patients), bronchoscopic biopsy (1 patient), and CT-guided needle biopsy (3 patients) (1 patient had a needle biopsy and wedge resection). In another 10 patients, pulmonary nodules were diagnosed as benign during clinical follow-up (range, 2-24 months; median, 11 months): in 1 patient, the nodule disappeared; in 1 patient, the nodule's size was stable; in 3 patients, the nodule's size decreased; and in 5 patients, no further radiological studies were performed, but no symptoms or signs of pulmonary disease were present during follow-up. Coccidioides immitis spherules were identified in 2 surgical specimens and in 1 CT-guided biopsy specimen. Serologic results for C immitis were positive for 3 patients: 1 at the time of lobectomy and 2 during clinical follow-up. CONCLUSION: The enhancing rim sign, seen on chest CT with intravenous contrast enhancement of a solitary pulmonary nodule, has been useful to distinguish some benign pulmonary nodules from malignant pulmonary nodules.

Aged↗

PubMed1992

Evaluation and management of solitary and multiple pulmonary nodules.

The evaluation and management of a patient with an SPN is guided by principles that were derived from earlier surgical studies. Stability or no growth for at least 2 years, the presence of calcium in characteristic patterns, and age less than 35 years without any associated risk factors are reliable indicators of a benign process. Fluoroscopy and localized tomography are helpful in evaluation of an SPN. If the nodule is still considered indeterminate, CT scanning, with the use of thin section cuts through the nodule, is now widely employed. If calcium is present in a characteristic pattern, the nodule is considered benign. If the nodule is very dense or more dense than a phantom reference nodule, the nodule has a high likelihood of being benign. Nodules that are less dense than the phantom nodule are indeterminate, and approximately 25% of these nodules will be benign. Computed tomography scan of the chest and upper abdomen is indicated in patients with a previous history of malignancy or when there is a high suspicion that the nodule is malignant. The further evaluation and management of SPNs that are indeterminate after CT examination are controversial. Some recommend tissue biopsy via transbronchoscopic or transthoracic approach, whereas others recommend immediate thoracotomy. Observation is indicated in certain situations when the chance of malignancy is quite low, the patient is not an operable candidate, or when the patient refuses further invasive evaluation. The physician's role in the management of a patient with an SPN is to educate and advise. The physician must be aware of the patient's anxieties, fears, and attitude and provide an opportunity for active participation by the patient in the decision-making process. Multiple pulmonary nodules are most commonly encountered in patients with metastatic disease to the lungs. Other less commonly encountered diseases that present as multiple pulmonary nodules include infections, arteriovenous malformations, Wegener's granulomatosis, and lymphoma. The evaluation and management of the patient with multiple pulmonary nodules are usually guided by the history, physical examination, and laboratory findings.

Adult↗

PubMed1993

[Evaluation of ultrasonography in the diagnosis of thyroid nodules].

Purpose of the paper: Specify the merits of ultrasonography in thyroid pathology. Outline ultrasonographic orienting criteria to identify the nature of thyroid nodules. Analysis of the paper: Thyroid ultrasonography allows detecting nodules that cannot be detected clinically or with radionuclide scanning. 20% of sonographic nodules cannot be palpated; 33% of sonographic nodules are not visible on radionuclide scans. Ultrasonography often shows multiple nodules where palpation and/or radionuclide scanning detect only one. When there are clinical signs of hyperthyroidism and uncertain biological findings, ultrasonography can relate a low-uptake nodule with an adenoma becoming autonomous, if the nodule appears to be hypodense. It allows monitoring the volume of nodules under freination therapy. Benign nodules may be liquid (15.7% of all cases); solid and isoechogenic (27.6%); solid and hyperechogenic (10.1%); solid and hypoechogenic (18.1%, including 88.5% toxic adenomas) or compound (26.4%). Comparison of the 2 series of nodules reveals the predominance of liquid and iso/hyperechogenic solid appearances for benign nodules (63.8%, excluding toxic adenomas). For cancers, the frequency of hypodense solid or compound nodules is 92.2%. Combining radionuclide scanning and ultrasonography allows further restricting the group of suspicious nodules, which have a low uptake and are hypodense or compound.

France↗

PubMed1996

Ultrasound-guided fine needle aspiration biopsy of small pulmonary nodules abutting to the chest wall.

BACKGROUND: Ultrasound (US)-guided needle biopsies in peripheral pulmonary lesions are widely applied. Most pulmonary lesions had a large size. We report our results in evaluating the availability of US-guided fine needle aspiration biopsy (US-guided FNAB) in diagnosing small pulmonary nodules abutting to the chest wall. METHODS: Forty patients, whose chest radiographs showed peripheral pulmonary nodules of diameter smaller than 3.0cm, received chest sonographic examination and US-guided FNAB. Of those, six patients had no definite diagnoses; the remaining 34 patients with pulmonary nodules, we divided into three groups. There were four tiny nodules of diameters smaller than 1.0cm, 11 nodules between 1.1 and 2.0cm, and 19 nodules between 2.1 and 3.0cm. We evaluated the diagnostic yields and rates of complication in relation to the size or nature of the nodule. RESULTS: In the enrolled 40 patients, six were lost to surveillance and had indeterminate diagnoses. Of the remaining 34 patients with proven pathological diagnoses and compatible clinical conditions, the diagnostic yields of US-guided FNAB achieved 88% (30/34) which include 96% (26/27) in malignancies and 57% (4/7) in benign nodules. According to the nodular size, the diagnostic rate achieved 100% (4/4) in tiny nodules, 91% (10/11) in nodules between 1.1 and 2.0cm, and 84% (16/19) in nodules between 2.1 and 3.0cm. Only one patient with a 2.5-cm nodule developed pneumothorax after the US-guided FNAB procedure. CONCLUSIONS: US-guided FNAB is a useful and safe diagnostic tool for small pulmonary nodules abutting to the chest wall. The nodular nature, but not size, affects the diagnostic yields and rates of complication.

Adult↗

PubMed2005

Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma.

In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver (EASL) recommendations, as a criterion for characterizing small (1-3 cm) nodules in cirrhosis. A total of 72 nodules (1-2 cm, n = 41; 2.1-3 cm, n = 31) detected by ultrasonography in 59 patients with cirrhosis were included in the study. When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography, the lesion was considered to be hepatocellular carcinoma (HCC) according to EASL criteria. When one or both techniques showed negative results, ultrasound-guided biopsy was performed. In cases with negative results for malignancy or high-grade dysplasia, biopsy was repeated when an increase in size was detected at the 3-month follow-up examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%; 44% of 1-2-cm nodules and 84% of 2-3-cm nodules). Fourteen nodules (19.4%) had negative results with both techniques (hypovascular nodules). Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion, the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of small nodules in cirrhosis; thus, biopsy frequently is required in this setting. Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as highly suspicious for HCC.

Aged↗

PubMed1987

The histopathology and biochemistry of phenobarbitone-induced liver nodules in C3H mice.

The sequential development of hepatic nodules induced by phenobarbitone (PB) has been studied in the C3H/He strain of mouse, a strain prone to the development of spontaneous liver tumours. PB was administered in the diet to young male animals at a dose level of 85 mg/kg/day for up to 91 weeks. Control and PB-treated mice developed hepatic nodules within 60 weeks. In control animals the nodules consisted of small basophilic cells, and by 80 weeks a small proportion of the animals had developed unequivocal hepatocellular carcinoma. The basophilic nodules were similar in many respects to those induced by N-nitrosodiethylamine. In PB-treated mice the incidence of basophilic nodules was similar to that in controls. These animals also developed hepatic nodules formed of large eosinophilic cells which were readily dissectable from the surrounding host tissue by 60 weeks. Biochemical investigations into the large eosinophilic nodules from PB treated mice showed that both Phase I and Phase II types of xenobiotic metabolizing enzyme activities were induced to levels either similar to, or greater than in the surrounding host tissue. In contrast, enzyme activities in basophilic nodules from untreated mice killed at 91 weeks, were generally similar to or lower than in the surrounding host tissue. The presence of eosinophilic nodules did not lead to an increase in the incidence of hepatocellular carcinoma in the PB-treated C3H/He mice. Concurrent experiments conducted in the C57BL/6 strain of mouse did not result in the development of liver nodules at 60 weeks. Thus, the eosinophilic nodules induced by phenobarbitone in C3H/He mice appear to be distinctly different from the basophilic liver nodules arising spontaneously or to basophilic nodules produced by the hepatocellular carcinogen N-nitrosodiethylamine.

Animals↗

PubMed1995

Expression of nodulin genes in plant-determined ineffective nodules of pea.

The mutant E135 (sym 13) of pea (Pisum sativum L.) forms a normal number of small white nodules that contain bacteroids, but these bacteroids lack nitrogenase activity. To evaluate the effects of the sym 13 gene on the expression of nodulin genes, cDNA clones for nodulins were isolated from pea nodules and the expression of nodulin genes in ineffective E135 nodules was compared with that in nitrogen-fixing nodules on the wild-type parent, cv. Sparkle. Nineteen cDNA clones for nodulins, including ENOD2 and cDNAs for two distinct leghemoglobins (Lbs), were isolated from Sparkle nodules by a subtractive hybridization procedure. All the nodulin genes examined were expressed in nodules on both E135 and Sparkle plants. However, the level of expression of seven genes, one of which was an Lb gene that corresponded to PsN5, was significantly lower in E135 nodules. The levels of Lb apo-proteins, with the exception of Lb-III and Lb-IV, in E135 nodules resembled those in Sparkle nodules, but the level of heme in E135 nodules was lower than that in Sparkle nodules. Although the expression of the two Lb genes that corresponded to PsN5 and PsN120 in E135 nodules was slightly depressed by exogenous ammonia, the level of the PsN5 transcript was still lower than the control level in Sparkle nodules. Our results indicate that the plant gene sym 13 does not influence the induction of nodulin genes but does influence the level of the expression of some genes, one of which is a gene for Lb, as well as the level of heme.

Ammonia↗

PubMed2001

Automatic detection of pulmonary nodules at spiral CT: clinical application of a computer-aided diagnosis system.

The aim of this study was to evaluate a computer-aided diagnosis (CAD) workstation with automatic detection of pulmonary nodules at low-dose spiral CT in a clinical setting for early detection of lung cancer. Eighty-eight consecutive spiral-CT examinations were reported by two radiologists in consensus. All examinations were reviewed using a CAD workstation with a self-developed algorithm for automatic detection of pulmonary nodules. The algorithm is designed to detect nodules with diameters of at least 5 mm. A total of 153 nodules were detected with at least one modality (radiologists in consensus, CAD, 85 nodules with diameter < 5 mm, 68 with diameter > or = 5 mm). The results of automatic nodule detection were compared to nodules detected with any modality as gold standard. Computer-aided diagnosis correctly identified 26 of 59 (38%) nodules with diameters > or = 5 mm detected by visual assessment by the radiologists; of these, CAD detected 44% (24 of 54) nodules without pleural contact. In addition, 12 nodules > or = 5 mm were detected which were not mentioned in the radiologist's report but represented real nodules. Sensitivity for detection of nodules > or = 5 mm was 85% (58 of 68) for radiologists and 38% (26 of 68) for CAD. There were 5.8+/-3.6 false-positive results of CAD per CT study. Computer-aided diagnosis improves detection of pulmonary nodules at spiral CT and is a valuable second opinion in a clinical setting for lung cancer screening despite of its still limited sensitivity.

Adult↗

PubMed1992

Association between growth stimulation by phenobarbital and expression of cytochromes P450 1A1, 1A2, 2B1/2 and 3A1 in hepatic hyperplastic nodules in male F344 rats.

This study was conducted to examine relationships between phenobarbital (PB) treatment, specific cytochrome P450 gene expression patterns and growth rates of hepatic hyperplastic nodules. Nodules were induced in 8 week old male F344 rats by a Solt-Farber resistance protocol. Six weeks after diethylnitrosamine (DEN) initiation, subgroups of rats were either kept on control chow diet or transferred to a chow diet containing 0.05% PB, then killed 2 weeks later. [3H]Thymidine was delivered continuously via osmotic minipump during the final 3 days of the experimental to label dividing cells. PB treatment resulted in a 89% increase in the number of persistent gamma-glutamyl transpeptidase (GTT) nodules per cm2 section, a 278% increase in the area of persistent GGT nodules per cm2 section, and a 116% increase in the average area per persistent nodule. PB increased the number of [3H]thymidine-labeled persistent GGT nodules but did not significantly change the labeling index (LI) distribution pattern or the average LI. A slight but uniform increase in CYP1A2 expression (relative to surrounding, non-nodular tissue) was observed in 50% (23/46) and 59% (60/102) of persistent nodules in control and PB-treated animals respectively. In contrast, for nodules undergoing remodeling, CYP1A2 expression was elevated in only 9% (2/22) and 0% (0/24) in control and PB groups respectively. In the PB group, CYP2B1/2 was underexpressed in 53% (54/102) of persistent GGT nodules and in 0% (0/24) of the remodeling nodules. Comparing LI among the persistent GGT nodules, those that displayed simultaneous increases in CYP1A2 and decreases in CYP2B1/2 had the highest LI, and were followed in level by those expressing either increases in CYP1A2 or decreases in CYP2B1/2. Nodules that expressed both CYP1A2 and 2B1/2 in a manner similar to the surrounding tissue had the lowest LI. Thus, these data suggest that expression of specific forms of cytochrome P450 may be an important factor in determining other phenotypic characteristics, e.g. rate of cell proliferation and GGT expression, within specific nodules.

Animals↗

PubMed2001

Redifferentiation of bacteria isolated from Lotus japonicus root nodules colonized by Rhizobium sp. NGR234.

In most studies concerning legume root nodules, the question to what extent the nodule-borne bacteroids survive nodule senescence has not been properly addressed. At present, there is no "model system" to study these aspects in detail. Such a system with Lotus japonicus and the broad host range Rhizobium sp. NGR234 has been developed. L. japonicus L. cv. Gifu was inoculated with Rhizobium sp. NGR234 and grown over a 12 week time period. The first nodules could be harvested after 3 weeks. Nodulation reached a plateau after 11 weeks with a mean of 64 nodules having a biomass of nearly 100 mg FW per plant. Nodules were harvested and homogenized at different stages of plant development. Microscopic inspection of the extracts revealed that, typically, nodules contained c. 15x10(9) bacteroids g(-1) FW, and that about 60% of the bacteroids were viable as judged by vital staining. When aliquots of the extracts were plated on selective media, a substantial number of "colony-forming units" was observed in all cases, indicating that a considerable fraction of the bacteroids had the potential to redifferentiate into growing bacteria. In nodules from the early developmental stages, the fraction of total bacteroids yielding CFUs amounted to about 20%, or one-third of the bacteroids judged to be viable after extraction, and it increased slightly when the plants started to flower. In order to see how nodule senescence affected the survival and redifferentiation potential of bacteroids, some plants were placed in the dark for 1 week. This led to typical symptoms of senescence in the nodules such as an almost complete loss of nitrogenase activity and a considerable decrease in soluble proteins. However, surprisingly, the number of total and viable bacteroids g(-1) nodule FW remained virtually constant, and the fraction of total bacteroids yielding CFUs did not decrease but significantly increased up to 75% of the bacteroids judged to be viable after extraction. This result indicates that during nodule senescence bacteroids might be induced to redifferentiate into the state of free-living, growing bacteria.

Colony Count, Microbial↗

PubMed2002

Dupuytren's disease: physiologic changes in nodule and cord fibroblasts through aging in vitro.

The pathogenesis of the fibrotic disease Dupuytren's contracture remains unclear. The disease process includes two structurally distinct fibrotic elements, the nodule and the cord. It has been proposed that as the disease progresses, nodules develop into cords. To corroborate that hypothesis, the authors took advantage of cultured fibroblast differences found between gap junction intercellular communication and fibroblast-populated collagen lattice contraction. Paired fibroblast cell lines of nodules and cords derived from four patients with Dupuytren's disease were maintained in culture for at least eight passages. The presence of gap junction intercellular communication in nodule- and cord-derived fibroblasts was documented and reported as a coupling index. The contraction of free-floating nodule- or cord-derived collagen lattices was also documented and reported. Early passage (passage 4) cord-derived fibroblasts showed a significant increase in coupling index compared with passage 4 nodule-derived fibroblasts (4.0 +/- 0.4 versus 2.5 +/- 0.3, respectively), where p < or = 0.01. However, late passage (passage 8) nodule- and cord-derived fibroblasts were equivalent in their coupling index (4.1 +/- 0.4 versus 4.4 +/- 0.4, respectively). Early passage nodule-derived fibroblast-populated collagen lattices contracted by 64 percent, whereas late passage nodule-derived lattices showed less contraction, at only 40 percent. Early and late passage cord-derived lattices contracted 46 and 37 percent, respectively. All nodule- and cord-derived cell lines were statistically equivalent at lattice contraction by passage 8. These in vitro studies support the hypothesis that fibroblasts derived from Dupuytren's contracture nodules change their phenotype after undergoing repeated cell passage, acquiring a cord-like fibroblast phenotype. Dupuytren's nodules represent the early, active form of fibrosis in which cells are more proliferative, better at fibroblast-populated collagen lattice contraction, and display less gap junction intercellular communication. The speculation is that alterations in gap junction intercellular communication may be involved in the progression of Dupuytren's nodules to cords as the disease progresses.

Cell Communication↗