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OBJECTIVE: We prospectively evaluated the effects of 12 months thyrotropin suppressive levo-thyroxine (L-T4) therapy in terms of changes in both thyroid nodule size and cytological features and considered whether thyroid nodule size changes actually resulted in (or were the result of) cytological changes. DESIGN AND PATIENTS: We studied 142 consecutive patients with benign 'cold' solitary thyroid nodules. For the purposes of the study, we divided our patients into three groups according to their initial cytological nodule classification as follows: group 1, including 88 colloid nodules (CN); group 2, including 30 hyperplastic nodules (HN); and group 3, including 24 adenomatous nodules (AN). MEASUREMENTS: The effects of TSH suppressive L-T4 treatment on both nodule volume and cytological characteristics were evaluated by ultrasonography and fine-needle aspiration (FNA) before and 12 months after the onset of therapy. RESULTS: Twelve months of TSH suppressive L-T4 treatment were effective in shrinking about one-third to one-quarter (31.8% CN, 26.7% HN and 25% AN) of thyroid nodules, irrespective of their initial cytological characteristics. Similarly, there was no difference in the prevalence of 'non-responders' (increasing nodules) to L-T4, which accounted for about one-fifth or less (20.5% CN, 13.3% HN and 20.8% AN) of all nodules. We found also that cytological features changed in 33.8% nodules after 12 months of L-T4 treatment. These changes were most commonly observed in HN and AN and consisted largely ( approximately 80%) of cytological characteristics resembling colloid features, not only in shrinking but also in stable nodules, thus indicating that cytology changes might be the very first indicator of nodule sensitivity to L-T4 therapy even in the continued absence of nodule shrinkage. When nodules were divided into three subgroups according to variations in size (shrinking, stable and increasing nodules), we observed that the distribution of the three cytological types showed a trend towards colloid lesions in shrinking nodules (chi2 3.8, P < 0.005) and towards an augmentation of hypercellular, adenomatous and suspicious characteristics in increasing nodules (chi2 3.6, P < 0.005). CONCLUSION: The frequency of shrinking nodules was not different between colloid, hyperplastic and adenomatous nodules. Repeat FNA should be advisable for thyroid nodules which increase in volume despite L-T4 therapy and might also provide useful information about nodule sensitivity to L-T4 treatment for both HN and AN, even where nodule size remains stable.
UNLABELLED: Macroregenerative nodules are commonly thought to be hyperplastic lesions, deriving both their large size and premalignant potential from an increased proliferative rate. We have previously suggested an alternate model of macroregenerative nodule development in which neither size nor premalignant potential of macroregenerative nodules would depend on increased proliferation. We tested this hypothesis by examining the proliferative activity in macroregenerative and surrounding cirrhotic nodules. METHODS: Eighteen macroregenerative nodules, including five type I and 13 type II, were immunostained for proliferating cell nuclear antigen (PCNA). Type II macroregenerative nodules included ten with diffuse large (7) or small (3) liver cell dysplasia only and eight containing nodule-in-nodule lesions. Five nodule-in-nodule lesions met the histologic criteria for hepatocellular carcinoma. PCNA labeling indices (PCNA-LIs; percentage positive hepatocyte nuclei/500 randomly counted cells) were determined in macroregenerative nodules and the four largest adjacent cirrhotic nodules. Nodule-in-nodule lesions were assessed separately from the background macroregenerative nodule. RESULTS: 4/5 type I and 12/13 type II macroregenerative nodules (exclusive of NIN lesions) had PCNA-LIs lower than the mean of surrounding cirrhotic nodules. All nodule-in-nodule lesions, whether atypical or overtly malignant, had PCNA-LIs greater than any surrounding nodules. In conclusion, macroregenerative nodules have PCNA-LIs indistinguishable from, and often lower than, surrounding cirrhotic nodules. Increased proliferative activity only occurs with the development of atypia and transition to hepatocellular carcinoma. CONCLUSION: Macroregenerative nodules derive neither their size nor their premalignant potential from on-going rapid proliferation, a finding consistent with our alternate hypothesis of macroregenerative nodule development.
In this study, we investigated a pattern-recognition technique based on an artificial neural network (ANN), which is called a massive training artificial neural network (MTANN), for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography (CT) images. The MTANN consists of a modified multilayer ANN, which is capable of operating on image data directly. The MTANN is trained by use of a large number of subregions extracted from input images together with the teacher images containing the distribution for the "likelihood of being a nodule." The output image is obtained by scanning an input image with the MTANN. The distinction between a nodule and a non-nodule is made by use of a score which is defined from the output image of the trained MTANN. In order to eliminate various types of non-nodules, we extended the capability of a single MTANN, and developed a multiple MTANN (Multi-MTANN). The Multi-MTANN consists of plural MTANNs that are arranged in parallel. Each MTANN is trained by using the same nodules, but with a different type of non-nodule. Each MTANN acts as an expert for a specific type of non-nodule, e.g., five different MTANNs were trained to distinguish nodules from various-sized vessels; four other MTANNs were applied to eliminate some other opacities. The outputs of the MTANNs were combined by using the logical AND operation such that each of the trained MTANNs eliminated none of the nodules, but removed the specific type of non-nodule with which the MTANN was trained, and thus removed various types of non-nodules. The Multi-MTANN consisting of nine MTANNs was trained with 10 typical nodules and 10 non-nodules representing each of nine different non-nodule types (90 training non-nodules overall) in a training set. The trained Multi-MTANN was applied to the reduction of false positives reported by our current computerized scheme for lung nodule detection based on a database of 63 low-dose CT scans (1765 sections), which contained 71 confirmed nodules including 66 biopsy-confirmed primary cancers, from a lung cancer screening program. The Multi-MTANN was applied to 58 true positives (nodules from 54 patients) and 1726 false positives (non-nodules) reported by our current scheme in a validation test; these were different from the training set. The results indicated that 83% (1424/1726) of non-nodules were removed with a reduction of one true positive (nodule), i.e., a classification sensitivity of 98.3% (57 of 58 nodules). By using the Multi-MTANN, the false-positive rate of our current scheme was improved from 0.98 to 0.18 false positives per section (from 27.4 to 4.8 per patient) at an overall sensitivity of 80.3% (57/71).
CONTEXT: Controversy remains as to the optimal management of patients with multiple thyroid nodules. OBJECTIVE: The objective of this study was to determine the prevalence, distribution, and sonographic features of thyroid cancer in patients with solitary and multiple thyroid nodules. DESIGN: We describe a retrospective observational cohort study that was carried out from 1995 to 2003. SETTING: The study was conducted in a tertiary care hospital. PATIENTS: Patients with one or more thyroid nodules larger than 10 mm in diameter who had ultrasound-guided fine needle aspiration (FNA) were included in the study. MAIN OUTCOME MEASURES: The main outcome measures were prevalence and distribution of thyroid cancer and the predictive value of demographic and sonographic features. RESULTS: A total of 1985 patients underwent FNA of 3483 nodules. The prevalence of thyroid cancer was similar between patients with a solitary nodule (175 of 1181 patients, 14.8%) and patients with multiple nodules (120 of 804, 14.9%) (P = 0.95, chi(2)). A solitary nodule had a higher likelihood of malignancy than a nonsolitary nodule (P < 0.01). In patients with multiple nodules larger than 10 mm, cancer was multifocal in 46%, and 72% of cancers occurred in the largest nodule. Multiple logistic regression analysis of statistically significant features demonstrates that the combination of patient gender (P < 0.02), whether a nodule is solitary vs. one of multiple (P < 0.002), nodule composition (P < 0.01), and presence of calcifications (P < 0.001) can be used to assign risk of cancer to each individual nodule. Risk ranges from a 48% likelihood of malignancy in a solitary solid nodule with punctate calcifications in a man to less than 3% in a noncalcified predominantly cystic nodule in a woman. CONCLUSIONS: In a patient with one or more thyroid nodules larger than 10 mm in diameter, the likelihood of thyroid cancer per patient is independent of the number of nodules, whereas the likelihood per nodule decreases as the number of nodules increases. For exclusion of cancer in a thyroid with multiple nodules larger than 10 mm, up to four nodules should be considered for FNA. Sonographic characteristics can be used to prioritize nodules for FNA based on their individual risk of cancer.
OBJECTIVE: Our objective was to evaluate the performance of a computer-aided detection (CAD) system for pulmonary nodule detection using low-dose screening CT images. MATERIALS AND METHODS: One hundred fifty consecutive low-dose screening CT examinations were independently evaluated by a radiologist and a CAD pulmonary nodule detection system (R2 Technology) designed to identify nodules larger than 4 mm in maximum long-axis diameter. All discrepancies between the two techniques were reviewed by one of another two radiologists working in consensus with the initial interpreting radiologist, and a "true" nodule count was determined. Detected nodules were classified by size, density, and location. The performance of the initial radiologist and the CAD system were compared. RESULTS: The radiologist detected 518 nodules and the CAD system, 934 nodules. Of the 1,106 separate nodules detected using the two techniques, 628 were classified as true nodules on consensus review. Of the true nodules present, the radiologist detected 518 (82%) of 628 nodules and the CAD, 456 (73%) of 628 nodules. All 518 radiologist-detected nodules were true nodules, and 456 (49%) of 934 of CAD-detected nodules were true nodules. The radiologist missed 110 true nodules that were only detected by CAD. In six patients, these were the only nodules detected in the examination, changing the imaging follow-up protocol. CAD identified 478 lesions that on consensus review were false-positive nodules, a rate of 3.19 (478/150) per patient. CONCLUSION: CAD detected 72.6% of true nodules and detected nodules in six (4%) patients not identified by radiologists, changing the imaging follow-up protocol of these subjects. In this study, the combined review of low-dose CT scans by both the radiologist and CAD was necessary to identify all nodules.
OBJECTIVE: In the Early Lung Cancer Action Project (ELCAP), we found not only solid but also part-solid and nonsolid nodules in patients at both baseline and repeat CT screening for lung cancer. We report the frequency and significance of part-solid and nonsolid nodules in comparison with solid nodules. MATERIALS AND METHODS: We reviewed all instances of a positive finding in patients at baseline (from one to six noncalcified nodules) and annual repeat screenings (from one to six newly detected noncalcified nodules with interim growth) to classify each of the nodules as solid, part-solid, or nonsolid. We defined a solid nodule as a nodule that completely obscures the entire lung parenchyma within it. Part-solid nodules are those having sections that are solid in this sense, and nonsolid nodules are those with no solid parts. Chi-square statistics were used to test for differences in the malignancy rates. RESULTS: Among the 233 instances of positive results at baseline screening, 44 (19%) involved a part-solid or nonsolid largest nodule (16 part-solid and 28 nonsolid). Among these 44 cases of positive findings, malignancy was diagnosed in 15 (34%) as opposed to a 7% malignancy rate for solid nodules (p = 0.000001). The malignancy rate for part-solid nodules was 63% (10/16), and the rate for nonsolid nodules was 18% (5/28). Even after standardizing for nodule size, the malignancy rate was significantly higher for part-solid nodules than for either solid ones (p = 0.004) or nonsolid ones (p = 0.03). The malignancy type in the part-solid or nonsolid nodules was predominantly bronchioloalveolar carcinoma or adenocarcinoma with bronchioloalveolar features, contrasting with other subtypes of adenocarcinoma found in the solid nodules (p = 0.0001). At annual repeat screenings, only 30 instances of positive test results have been obtained; seven of these involved part-solid or nonsolid nodules. CONCLUSION: In CT screening for lung cancer, the detected nodule commonly is either only part-solid or nonsolid, but such a nodule is more likely to be malignant than a solid one, even when nodule size is taken into account.
The fate of benign thyroid nodules has been unknown because there has been no study in this regard. We re-examined 134 patients with thyroid nodules who had had benign aspiration biopsy cytology 9 to 11 years ago. The thyroid gland was palpated by the same two thyroidologists throughout the study. Ultrasonography, fine-needle aspiration biopsy (FNAB), and ultrasound-guided FNAB were employed to examine the nature of nodules of 9 to 11 years' duration. Patients (n = 61) who had nodules difficult to palpate (small nodules), multiple nodules, or cystic nodules with papillomatous proliferation underwent ultrasound-guided FNAB; patients (n = 55) having a distinctly palpable single nodule underwent usual FNAB. None of the patients received any medical or surgical treatment. There were 86 single nodules, 14 multiple nodules, and 34 cystic nodules on the first examination. These benign nodules were reexamined for changes in size and cytology 9 to 11 years later. The most striking finding was a decrease in size or disappearance of the nodule in 42% to 79% of benign nodules. About 92% of nodules remained benign without changing cytologic classification. Only one case (0.9%) previously regarded as benign turned out to be malignant; this nodule grew in size compared with the previous examination. Among single and multiple nodules, 21% to 23% of the nodules increased in size; however, most patients with enlarged nodules (86%) showed the same class 2 cytology as before. Our present study indicates that biopsy-proved benign thyroid nodules remain benign over a prolonged period. Thus no medical or surgical treatment is required so long as the nodules do not grow.