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Video-assisted thoracoscopic surgery for pulmonary nodules after computed tomography-guided marking with a spiral wire.

PURPOSE: Peripheral pulmonary nodules are preferably removed by minimally invasive techniques, such as video-assisted thoracoscopic (VATS) surgery. These nodules should be marked preoperatively for better intraoperative detection and removal. DESCRIPTION: Twenty-two cases with a single pulmonary nodule requiring surgical removal for histologic examination were included in a prospective study. Guided by computed tomography, nodules were marked preoperatively using a laser marker system and fixed with a spiral wire. The marked nodules were removed by VATS surgery immediately after the marking. EVALUATION: The marking wire was placed in all 22 patients without any complications. The marked nodule was completely removed by VATS surgery in 19 patients. Conversion to thoracotomy was necessary in 3 patients, twice because of thoracoscopy-related problems and once because of a marking failure. The average times for the marking procedure and operation were 24 minutes and 32 minutes, respectively. CONCLUSIONS: This new method of computed tomography-guided nodule marking with a spiral wire and subsequent VATS surgery is very efficient in terms of localization and stable fixation of subpleural pulmonary nodules.

Adult↗

Thoracoscopic localization techniques for patients with solitary pulmonary nodule and history of malignancy.

BACKGROUND: Our aim was to evaluate the best intrathoracoscopic localization technique in patients with single pulmonary nodule and a history of malignancy. METHODS: We divided 50 patients in two groups, well matched for diameter and depth of the pulmonary lesion. In 25 patients we performed intrathoracoscopic ultrasound to locate the pulmonary nodule (group A), whereas in the other 25 patients the radio-guided technique was adopted (group B). In both group A and group B, the localization techniques were compared with finger palpation. In group A, 12 nodules were in the left lung and 13 in the right one; in group B, 11 lesions were in the left and 14 in the right lung. In both groups, the distance of the nodule from the pleural surface was 2.6 +/- 0.5 cm (2 to 2.5 cm in 14 patients, and >2.5 cm for the remaining 11). The diameter of the nodule was 1.26 +/- 0.22 (< or =1 cm in 10 patients, and 1 to 1.5 cm in 15) in both groups. All patients underwent thoracoscopic wedge resection, and 10 patients with a primary pulmonary lesion underwent posterior-lateral thoracotomy for lobectomy and mediastinal lymphadenectomy. RESULTS: In group A, ultrasound localized the nodule in 24 of 25 patients (96%) whereas finger palpation localized it in 19 of 25 (76%; not significant). In group B, both the radio-guided and finger palpation techniques localized the nodule in 20 of 25 patients (80%; not significant). No complications were recorded with the ultrasound technique; however, 10 cases of pneumothorax were detected after the radio-guided technique (p < 0.01). CONCLUSIONS: Both the ultrasound and radio-guided techniques are accurate to detect solitary pulmonary nodules, but the radio-guided method yields complications as compared with the ultrasound.

Adenocarcinoma↗

Ultrasonographic evaluation of small nodules in the peripheral lung during video-assisted thoracic surgery (VATS).

OBJECTIVE: We examined the possibility of intraoperative ultrasonography during video-assisted thoracic surgery (VATS) to localize and make a qualitative diagnosis of small peripheral pulmonary nodules. METHODS: Ultrasonography during VATS and conventional thoractomy was performed on 25 and 18 nodules, respectively, all which were localized in the peripheral lung, were less than 30 mm in diameter and for which there was no definitive diagnosis. RESULTS: All 25 nodules, including 10 invisible but palpable and three both invisible and non-palpable, could be localized by ultrasonography during VATS. If nodules were located less than 15 mm from the pleural surface, ultrasonography during VATS could detect nodules 10 mm or less in diameter. The rate of malignant tumors among 11 of 12 pulmonary nodules (91.6%) showing both heterogeneous and ill-defined patterns was significantly higher than 6 of 16 nodules (37.5%) showing both homogeneous and well-defined patterns on ultrasonography. CONCLUSIONS: Our study suggested that ultrasonography during VATS is useful for the detection of peripheral pulmonary nodules, even when they are not identified on video images or palpation, and may enable a differential diagnosis between malignant and non-malignant lesions.

Adult↗

Influence of rib structure on detection of subtle lung nodules.

PURPOSE: To access the influence of anatomic noise on the detectability of subtle lung nodules depicted on chest radiographs. MATERIAL AND METHODS: From normal chest radiography images, 132 square regions were extracted, of which the centers were on the upper margin of a rib, the inside of a rib, the lower margin of a rib, and the central region between two adjoining ribs. Simulated nodules were digitally superimposed at the centers of these extracted square images. Twelve radiologists viewed 50 soft-copy images consisting of these 792 processed images, including the noise-added images. The observer's confidence level for the square images containing single nodules was used as an index of observer performance. RESULTS: Results indicated statistically reliable effects of the relationship between rib structures and nodule positions on the detection performance (P < 0.001). The nodule detectability on the images with a center located between two adjoining ribs was significantly the best, whereas it was significantly the worst on the noise-added images with a center located between two adjoining ribs. CONCLUSION: The rib structures overlying a subtle lung nodule on chest X-ray images have a detrimental effect on nodule detection performance as anatomic noise, regardless of the nodule location on ribs.

Adult↗

A computer-aided diagnosis system for detection of lung nodules in chest radiographs with an evaluation on a public database.

A computer algorithm for nodule detection in chest radiographs is presented. The algorithm consists of four main steps: (i) image preprocessing; (ii) nodule candidate detection; (iii) feature extraction; (iv) candidate classification. Two optional extensions to this scheme are tested: candidate selection and candidate segmentation. The output of step (ii) is a list of circles, which can be transformed into more detailed contours by the extra candidate segmentation step. In addition, the candidate selection step (which is a classification step using a small number of features) can be used to reduce the list of nodule candidates before step (iii). The algorithm uses multi-scale techniques in several stages of the scheme: Candidates are found by looking for local intensity maxima in Gaussian scale space; nodule boundaries are detected by tracing edge points found at large scales down to pixel scale; some of the features used for classification are taken from a multi-scale Gaussian filterbank. Experiments with this scheme (with and without the segmentation and selection steps) are carried out on a previously characterized, publicly available database, that contains a large number of very subtle nodules. For this database, counting as detections only those nodules that were indicated with a confidence level of 50% or more, radiologists previously detected 70% of the nodules. For our algorithm, it turns out that the selection step does have an added value for the system, while segmentation does not lead to a clear improvement. With the scheme with the best performance, accepting on average two false positives per image results in the identification of 51% of all nodules. For four false positives, this increases to 67%. This is close to the previously reported 70% detection rate of the radiologists.

Algorithms↗

Efficacy of thyroid hormone suppression for benign thyroid nodules: meta-analysis of randomized trials.

OBJECTIVE: To determine the efficacy of thyroid hormone suppressive therapy (THST) to decrease benign thyroid nodule volume. DESIGN: Meta-analysis. METHODS: Systematic search using electronic databases (PubMed, Medline, Cochrane Library) through August 2004, paper review, and contacting experts and drug manufacturers. Only randomized controlled studies of THST vs no treatment or placebo, for reduction of benign thyroid nodule volume, were included. Exclusion criteria were: <6-month treatment, lack of ultrasound volume measurement, and region of endemic goiter. Primary outcome was clinically relevant nodule volume reduction (>50%), with a random effects model (RevMan4.2). RESULTS: Nine randomized trials were included (609 subjects). Subjects were 88% more likely to experience >50% nodule volume reduction with THST than placebo or no treatment (relative risk = 1.88; 95% CI = 1.18-3.01; P = 0.008). However, 8 subjects must be subjected to the risk of cardiac and skeletal side effects from THST, for one to benefit from therapy (number needed to treat = 8, risk difference = 0.13; 95% CI = 0.06-0.19; P = 0.0003). Sensitivity analysis reveals that 15 null studies would have to have been missed to reverse statistical significance (fail-safe N = 15). Review of the only study with long-term treatment (5 years) suggests no significant difference in nodule volume reduction between THST and placebo. Further, studies with follow-up after THST withdrawal demonstrate rapid increase in thyroid nodule and goiter volumes. CONCLUSION: THST appears more likely than placebo or no treatment to significantly reduce benign thyroid nodule volume, but long-term treatment may be less effective and regrowth is likely following cessation of therapy. Given the risks of THST, routine use is not recommended for benign nodules.

Humans↗

Fluoroscopy-aided thoracoscopic resection of pulmonary nodule localized with contrast media.

BACKGROUND: The pulmonary nodules have become the major indication of video-assisted thoracic surgery (VATS). Recently, several preoperative or intraoperative techniques for identifying small or deeply seated pulmonary nodules have facilitated thoracoscopic resection. We describe the new technique for detecting difficult lesions. METHODS: Preoperatively, we marked the visceral pleura near the pulmonary nodules with dye, simultaneously injected contrast media (1 water-soluble Optiray [Mallinckrodt Medical Inc, Quebec, Canada], 18 barium sulfate, 11 Lipiodol [Laboratoire Guerbet, Aulnay-sous-Bois, France]) into or around the nodule under computed tomography (CT) guidance. During VATS, we were able to easily and accurately detect and resect all the nodules localized with contrast media, of which the radiopacity was visualized on the portable fluoroscopic monitor. RESULTS: Between February 1996 and December 1998, we thoracoscopically resected 30 nodules in 28 patients (13 were women; age, 53 +/- 14 years). The resected nodules were 17 +/- 7.6 mm (range; 4 to 32 mm) in size, and 8.9 +/- 8 mm (range, 2 to 34 mm) in depth. The pathologic diagnosis of the nodules was benign in 20 and malignant in 10 (six primary cancers of lung and four metastatic cancers). There were only minor complications related CT localization. CONCLUSIONS: This new technique can help the surgeons detect and resect the difficult lesions with safety and rapidity by VATS without thoracotomy.

Adult↗

Large cystic/solid thyroid nodules: a potential false-negative fine-needle aspiration.

BACKGROUND: False-negative fine-needle aspiration (FNA) biopsy results of thyroid nodules are of particular concern because they imply missed malignant lesions. The purpose of this study was to identify characteristics of thyroid nodules that may lead to false-negative cytologic interpretation after FNA. METHODS: We reviewed 90 consecutive patients who underwent preoperative FNA of thyroid nodules followed by thyroid surgery during a period of 27 months, including their clinical data, type and size of thyroid nodule, FNA cytology results, and final pathology report of the surgical specimen. RESULTS: Thyroid nodules that had the highest probability of malignancy were those that were large (3 cm or larger), cystic/solid, or large and cystic/solid. The overall false-negative rate for preoperative FNA was 11%. Large, cystic/solid, and thyroid nodules with both characteristics had false-negative rates of 17%, 25%, and 30%, respectively, compared with 0%, 9%, and 17% for small (less than 3 cm), solid, and solid nodules 3 cm or larger, respectively. CONCLUSIONS: Because of the high prevalence of malignancy in thyroid nodules that are large (3 cm or larger), cystic/solid, or large and cystic/solid and the high false-negative rate of FNA in diagnosing these lesions, thyroid lobectomy for diagnosis should be strongly considered in these patients even when FNA cytologic finding is interpreted as benign.

Adolescent↗

CT-guided methylene-blue labelling before thoracoscopic resection of pulmonary nodules.

OBJECTIVE: Evaluation of the efficiency of our technique of methylene-blue labelling of pulmonary nodules to facilitate thoracoscopic recognition and excision. DESIGN: Patients with a peripheral pulmonary nodule smaller than 2.5 cm and not in contact with the visceral pleura were included. Under tomodensitometric guidance, the nodules were labelled with methylene-blue within hours before thoracoscopic wedge resection. If frozen section revealed a primary bronchial carcinoma, thoracotomy and classical resection were performed during the same anesthesia. RESULTS: Between July 1992 and August 1996, 54 nodules were removed in 51 patients. Labelling was performed between 75 and 270 min before surgery and was complicated in 13 patients (25.4%) by a small pneumothorax without any clinical consequence. Labelling allowed successful thoracoscopic recognition of 50 nodules (92%) and thoracoscopic wedge resection was possible in all but one cases (91%). Five patients (9%) required thoracotomy. Histology showed a benign lesion in 22 cases, a primary lung carcinoma in 17 and a metastases in 15. Twenty of the 22 benign nodules (91%) were removed without thoracotomy. According to the protocol, 13 patients with a primary lung tumour underwent lobectomy during the same session. There was no mortality nor morbidity amongst patients who had thoracoscopy only. CONCLUSIONS: Our technique of labelling peripheral pulmonary nodules with methylene-blue is very effective and is not associated with any relevant complication. Thoracoscopic excision and diagnosis is possible in more than 90% of the cases. We therefore recommend this simple, low-cost and reliable technique for nodules not in contact with the visceral pleura before thoracoscopic wedge resection.

Adult↗

Fractal texture analysis in computer-aided diagnosis of solitary pulmonary nodules.

RATIONALE AND OBJECTIVES: The authors investigated the use of fractal texture characterization to improve the accuracy of solitary pulmonary nodule computer-aided diagnosis (CAD) systems. METHODS: Thirty chest radiographs were acquired from patients who had no pulmonary nodules. Thirty regions were selected that were considered remotely suspicious-looking for nodules. Artificial nodules of multiple shapes, sizes, and orientations were added at subtle levels of contrast to 30 non-suspicious-looking regions of the radiographs. Fractal dimensions of the 60 "nodule candidates" were calculated to quantify the texture of each region. Four radiologists also interpreted the images. RESULTS: The fractal dimension of each possible nodule provided statistically significant (P < .05) differentiation between regions that contained an artificial nodule and those that did not. The area under the receiver operating characteristic curve for the fractal analysis was significantly better (P < .05) than that for the radiologists. CONCLUSION: Fractal texture characterization provides useful information for the classification of potential solitary pulmonary nodules with CAD algorithms.

Diagnosis, Computer-Assisted↗

Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients.

UNLABELLED: Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN). OBJECTIVE: In this study we have defined the long-term efficacy and safety of PEI for the treatment of ATN, and we have attempted to optimize the clinical usefulness and improve the technical approach to PEI treatment. PATIENTS: One hundred and seventeen patients with ATN, 26 males and 91 females, aged 48 +/- 12.9 years (mean +/- SD), were offered PEI when other established treatments were refused or contraindicated. Seventy-seven patients were affected by toxic adenoma (60 with a single nodule, 17 with a multinodular goitre); 40 patients suffered from a pretoxic single nodule. METHODS: Sterile 95% ethanol was administered weekly under sonographic control by a 20-22 gauge needle without anaesthesia or pharmacological sedation. During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. According to hormone and scintigraphic data, three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra-nodular tissue uptake, along with elevated free T4 (FT4) and free T3 (FT3) and undetectable TSH levels); partial cure (normalization of FT4 and FT3 levels, with low/ undetectable TSH levels; persistent suppression of extra-nodular uptake); complete cure (normal thyroid hormone and TSH levels; restored extra-nodular uptake). RESULTS: The patients were followed for up to 5 years (median 2.5). PEI therapy was well tolerated by all patients. Complete cure was achieved in all pretoxic patients and in 60 (77.9%) patients with toxic adenoma, while partial cure was observed in 7 cases (9.1%) and failure in 10 (13%). PEI treatment proved similarly effective in toxic patients with a single nodule or with multinodular goitre (87 vs 88.2%, respectively). At the end of treatment, a significant shrinkage of nodule volume was observed in all patients (P = 0.0001). Toxic patients with pretreatment volume > 40 ml (n = 8) did not show a significant difference in treatment response rate as compared to those with volume < 40 ml. Recurrence of hyperthyroidism was never observed during follow-up, independently of thyroid status before treatment. Only one patient with significant thyroid autoantibody serum levels before PEI treatment, developed sub-clinical hypothyroidism at 3 years. The administration of methimazole and/or propranolol did not modify PEI outcome. CONCLUSION: Our data confirm the efficacy and safety of percutaneous ethanol injection for the therapy of autonomous thyroid nodules. The very low incidence of hypothyroidism along with the absence of recurrence of hyperthyroidism suggests that percutaneous ethanol injection is the treatment of choice in patients with pretoxic thyroid adenoma. Percutaneous ethanol injection appears an effective alternative procedure in toxic patients with a high surgical risk even if they have large nodules, and in younger ones in whom radioiodine is contraindicated. Patients may be submitted to anti-thyroid drug and/or beta-blocker therapy if it is necessary, but this does not affect percutaneous ethanol injection treatment outcome. Finally, not only single autonomous thyroid nodules but also toxic multinodular goitre may be successfully treated by percutaneous ethanol injection.

Adenoma↗

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

AIMS: A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. METHODS AND RESULTS: Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. CONCLUSION: TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

Acute Disease↗

Long-term follow up of serum thyroglobin levels and its clinical implications in subjects after surgical removal of "cold" thyroid nodule.

Increased thyroglobulin (Tg) serum level in females (n = 49) suffering from scintigraphically "cold" thyroid nodule (395 +/- 168, micrograms/l, mean +/- SD) is significantly higher (p less than 0.001) in comparison with the data obtained from euthyroid healthy persons (28 +/- 10, n = 15) or those diagnosed with scintigraphically functional thyroid nodule (72 +/- 14, n = 15). No correlation between Tg and TSH serum levels has been seen before surgical removal of "cold" nodule (rxy = +0.34). In 49 out of 75 cases (65.3%) struma colloids were confirmed pathohistologically. After surgery, "cold" thyroid nodule was removed, serum Tg level decreased progressively within several days and three months afterwards, Tg level in most patients was mainly within the normal range for a healthy subject. The positive correlation between Tg and TSH was established three months after surgical removal of the nodule (rxy = +0.90). An elevation of serum Tg level was found in 16 out of the 49 patients during different postoperative periods (from 2 to 9 years). Under thyroxine treatment, in most of these patients a significant decrease of serum Tg level was observed. However, in a few treated patients, no change in Tg level was seen. Further clinical control in thyroxine-nonsuppressive patients discovered a compensatory hypertrophy of thyroid tissue and the appearance of a new thyroid nodule later. Present data and clinical experience suggest that long-term follow-up of serum Tg level in patients after surgical removal of "cold" thyroid nodule, brings about to early diagnosis of thyroid tissue postoperative hypertrophy before the appearance of thyroid gland nodule relapse.

Adult↗

[Imaging diagnosis of solitary pulmonary nodules on an open low-field MRI system--comparison of two MR sequences with spiral CT].

OBJECTIVE: To evaluate and compare two fast gradient-echo sequences (GRE) concerning the visualization of solitary pulmonary nodules with an open low-field MRI system in comparison to computed tomography. MATERIALS AND METHODS: Fourteen patients with solitary pulmonary nodules detected by spiral CT ranging in size from 6 mm to 42 mm (mean 20 mm) underwent MRI on an open 0.2 T scanner using a spoiled 2D GRE (2D FLASH; TR/ TE/Flip = 100 ms/7.5 ms/30 degrees ) and a totally refocused 2D steady-state GRE (True-FISP; TR/TE/FA = 7.3 ms/3.5 ms/80 degrees ). The image quality concerning artifacts (by flow, breathing and susceptibility) and the morphologic characteristics of the nodules were scored and compared with CT by two independent radiologists. The diameters of the nodules measured by MRI were compared with CT measurements. The sequences were also evaluated with regard to the signal-to-noise ratio (SNR) of the lesion. RESULTS: All lesions were detected with the 2D FLASH sequence. True-FISP failed to find a granuloma with a size of 6 mm. The 2D FLASH was rated significantly superior to true FISP concerning image quality artifacts by susceptibility as well as concerning to CT the presentation of nodule characteristics. In MR images, the size of lesions was significantly smaller than in CT images for both sequences: for 2D FLASH the mean difference was 0.9 mm and for true FISP 2.6 mm. The SNR of the nodules was significantly higher for the 2D FLASH than for the true FISP. CONCLUSION: In low field MRI, the 2D FLASH sequence is superior to the 2D true FISP sequence in imaging of pulmonary nodules. With the 2D FLASH sequence nodules of 6 mm or larger in size can be visualized.

Aged↗

[Success and complication rate of CT-guided marking of pulmonary nodules with coil wires for video-assisted thoracoscopic surgery (VATS)].

PURPOSE: To assess the success and complication rate of the CT-guided marking of pulmonary nodules for video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: Pulmonary nodules (mean diameter 9 +/- 5 mm, mean pleural distance 7 +/- 5 mm) were marked with a coil wire in 30 patients (20 males, mean age 57.6 +/- 15.5 years, 22 patients with a history of malignancy). The intended coil-nodule distance was < or = 10 mm. RESULTS: 81 % of nodules were not visible by thoracoscopy. The technical success rate of CT-guided marking was 86.7 %. The projected nodule-coil distance was achieved in 90 % of cases. The procedure had to be changed from thoracoscopy to thoracotomy in 4 patients due to coil wire marking problems: 2 x coil displacement, 1 x coil-nodule distance > 10 mm, unfavorable direction of wire. Histology was determined in all patients (70 % malignant, 30 % benign). Complications requiring therapy were not observed. CONCLUSIONS: The CT-guided marking of pulmonary nodules is a precondition for VATS if the nodule does not involve the visceral pleura in the majority of cases. The success rate is high with a low complication rate.

Adult↗

US-guided fine-needle aspiration biopsy of thyroid nodules.

PURPOSE: To determine which nodular areas provide most adequate and accurate material for cytology during US-guided fine-needle aspiration biopsy (FNAB) of thyroid nodules. MATERIAL AND METHODS: In a prospective multicentre study, US-guided FNAB (0.8 mm) was performed in 342 thyroid nodules (338 patients, 285 women, 18-83 years, 285 palpable). Histology was obtained in 169 nodules, revealing 75 neoplasms (44.4%) including 18 cancers (10.7%). In 206 solid nodules, 2 passes (central and peripheral) were compared. In 82 complex nodules, 2 passes (solid area and cystic area) were compared. RESULTS: The inadequacy rate was 16.4% and the false-negative rates were 2.2% and 28.1% for the diagnosis of cancer and neoplasm, respectively. In solid nodules, material was more adequate with peripheral passes compared to central passes, but the difference was not significant. In complex nodules, the inadequacy rate was much higher for passes in cystic areas (80.5%) compared to passes in solid areas (46.3%). CONCLUSION: Cystic areas due to degeneration seldom provided adequate material when aspirated. Aspiration should always be obtained from solid areas, at best using US-guidance. Adenomas and non-neoplastic nodules were difficult to distinguish.

Biopsy, Needle↗

Cold thyroid nodules show a marked increase in proliferation markers.

Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.

Biomarkers↗

Is percutaneous ethanol injection a useful alternative for the treatment of the cold benign thyroid nodule? Five years' experience.

We describe our 5-year experience with percutaneous ethanol injection (PEI) for the treatment of cold benign thyroid nodules and report its efficacy and side effects. Fifty-four euthyroid outpatients (aged 44.8+/-12.7 years, mean+/-SD) were divided into two groups matched for sex, age, and nodule volume: 27 patients treated only by PEI and 27 patients treated additionally with levothyroxine-suppressive therapy (median follow-up: 24 months, range 6-48). Mean pretreatment nodule volume was 21.0 mL (range 5.4-54.6). Ethanol (1.3+/-0.6 mL/mL nodule volume) was injected under sonographic control in 4 to 13 weekly sessions (mean 7.4). PEI therapy was well tolerated by all patients. At the end of treatment, nodule volume was 7.7+/-5.7 mL (p = .0001). A further significant shrinkage was obtained at 1-year follow-up (4.4+/-3.8 mL; p < .05). No significant differences in nodule reduction were observed between the levothyroxine treated or untreated group and between patients with pretreatment nodule volume smaller or larger than 15 mL. Our study confirms the efficacy and safety of PEI in inducing volume shrinkage of cold benign thyroid nodules. Overall our data suggest that PEI may become an interesting alternative for patients with surgical indications, if they refuse surgery or are poor surgical risks, or eventually demand treatment for aesthetic purposes. It may also be considered when levothyroxine therapy is contraindicated or ineffective.

Administration, Cutaneous↗