Frequency and severity of globus pharyngeus symptoms in patients undergoing thyroidectomy: a pre-post short term cross-sectional study.

BACKGROUND: Globus pharyngeus is a sensation of a lump or foreign body in the throat, sometimes associated with thyroid diseases and surgery. Previous studies investigated this condition with contradictory results, mainly because not standardized instruments of measure were used. The aim of this study was to evaluate the prevalence and severity of globus pattern symptoms in a population of patients three months after a thyroidectomy, and the reduction or increase of pre-existing symptoms or the onset of new symptoms. METHODS: Ninety-five patients (65 women, 30 men, mean age 56.03 ± 12.45) were assessed for globus pattern symptoms before and three months after thyroid surgery (72 patients: benign goiter, 23 patients: papillary cancer). The Glasgow-Edinburgh Throat Scale (GETS) was translated into Italian and used as a validated instrument of measure of the severity of globus pattern symptoms. RESULTS: The Italian version of the GETS was reliable (Cronbach alpha = 0.85) and valid. Normative data were used to classify patients into 4 groups of severity. A significant decrease of the mean GETS score was observed at the postoperative assessment (13.02 ± 11.84 vs 8.00 ± 11.26; p < 0.01), but beside symptomatic patients who improved we could observe also two other significant groups of patients: asymptomatic patients who developed symptoms and symptomatic patients who remained symptomatic. CONCLUSIONS: The significant decrease of the mean GETS postoperative score was mainly due to the improvement of strongly symptomatic patients. Two other significant outcomes exist and further studies are needed to understand their pathophysiological mechanism.

Quality of scar after total thyroidectomy: a single blinded randomized trial comparing octyl-cyanoacrylate and subcuticular absorbable suture.

Objective. To compare the quality of resulting scar at 6 weeks after total thyroidectomy with the use of the tissue adhesive octyl-cyanoacrylate or subcuticular absorbable suture for the closure of cervicotomy. Material and Methods. There are 50 patients undergoing a cervicotomy for total thyroidectomy. Twenty-five patients were randomly assigned to closure with tissue adhesive and 25 with subcuticular absorbable suture. At week 6 the scar was evaluated by blinded assessors with the Italian version of POSAS questionnaire, a validated wound scale composed of an observer's and a patient's subscale. Results. Assessment of scar appearance showed a statistically significant difference (p = 0. 038) in favor of subcuticular suture with respect to tissue adhesive on observer's assessment. The difference on patients' self-assessment was not significant. A multivariate analysis of six qualitative features of scars showed a significant influence on assessment for hyperpigmentation and relief of scar. The Italian version of POSAS proved to be reliable. Conclusion. Though tissue adhesive represents a valid method of skin closure, subcuticular absorbable suture provides a better aesthetic outcome in small cervical incisions in the early phase after thyroid surgery.

Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology.

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the "Sapienza" University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient's thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule's malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients' presurgical selection.

HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells.

Experimental and epidemiological studies have revealed that chronic inflammation contributes to cancer progression and even predisposes to cellular transformation. Inflammatory infiltrates in papillary thyroid cancer include lymphocytes, macrophages and cytokines. High-mobility group box 1 protein (HMGB1) is a late inflammatory cytokine that signals danger to the immune system through the receptor for advanced glycation end-products (RAGE) and Toll-like receptor. The activation of the above receptors results in the secretion of growth, chemotactic and angiogenic factors that contribute to chronic inflammation. In this study, we suggest that apart from the activation of signal transduction pathways by the activation of RAGE, the indirect inhibition of cell cycle regulators [such as phosphatase and tensin homolog (PTEN)] may also cause an increase in cell growth and motility. MicroRNAs (miRNAs) have increasingly been implicated in regulating the malignant progression of cancer. MiR-221 and miR-222 have been found to be deregulated in human papillary thyroid carcinomas. They are involved in cell proliferation through the inhibition of the cell cycle regulator, p27kip1, in human papillary carcinomas. In this study, we show that HMGB1 increases the expression of miR-221 and miR-222 in primary cultures of excised papillary lesions and in an established papillary cancer cell line (BC PAP). The overexpression of oncogenic miR-221 and miR-222 caused by HMGB1 is associated with an increase in malignancy scores, namely cell growth and motility.

Factors influencing the length of the incision and the operating time for total thyroidectomy.

BACKGROUND: The incision used for thyroid surgery has become shorter over time, from the classical 10 cm long Kocher incision to the shortest 15 mm access achieved with Minimally Invasive Video-Assisted Thyroidectomy. This rather large interval encompasses many different possible technical choices, even if we just consider open surgery.The aim of the study was to assess the correlation between incision length and operation duration with a set of biometric and clinical factors and establish a rationale for the decision on the length of incision in open surgery. METHODS: Ninety-seven consecutive patients scheduled for total thyroidectomy were prospectively evaluated. All operations were performed by the same team and the surgeon decided the length of the incision according to his personal judgement. Patients who had previously undergone neck surgery were excluded. RESULTS: The length of the incision was strongly correlated with gender, thyroid volume, neck circumference and clinical diagnosis and weakly correlated with the body mass index. Operation duration was only weakly correlated with gender and neck circumference. Multiple linear regression revealed that the set of factors assessed explained almost 60 % of the variance in incision length but only 20 % of the variance in operation duration. When patients were classified according to the distribution of their thyroid volume, cases within one standard deviation of the mean did not show a significant difference in terms of operation duration with incisions of various lengths. CONCLUSIONS: Although thyroid volume was a major factor in driving the decision with respect to the length of the incision, our study shows that it had only minor effect on the duration of the operation. Many more open thyroidectomies could therefore be safely performed with shorter incisions, especially in women. Duration of the operation is probably more closely linked to the inherent technical difficulty of each case.

Nulliparity enhances the risk of second primary malignancy of the breast in a cohort of women treated for thyroid cancer.

BACKGROUND: Many studies have reported an increased risk of developing a second primary malignancy (SPM) of the breast in women treated for thyroid cancer. In this study, we investigated several potential risk factors for this association. The aim of this retrospective cohort study was to identify a subgroup of women surgically treated for papillary thyroid cancer that may benefit from more careful breast cancer screening. METHODS: A total of 101 women surgically treated for papillary thyroid cancer from 1996 to 2009 with subsequent follow-up were interviewed by phone regarding personal risk factors and lifestyle habits. Only 75 questionnaires could be evaluated due to a 25.7% rate of patients not retrieved or refusing the interview. Data analysis was performed using a multivariate logistic model. RESULTS: The standardised incidence ratio (SIR) for breast cancer was 3.58 (95% IC 1.14 - 8.37). Our data suggest a protective effect of multiparity on the development of a SPM of the breast (O.R. 0.15; 95% IC 0.25 - 0.86). Significant associations were not found with other known risk factors including Body Mass Index (BMI), age at first tumour, concurrent metabolic diseases, smoking, physical activity and familiarity. CONCLUSIONS: This study confirms that a higher incidence of SPM of the breast is observed in women treated for papillary thyroid cancer. Additionally, this risk is increased by nulliparity, thus a strict breast screening program for nulliparous women treated for thyroid cancer may be advisable.

Cross-talk between NO and HMGB1 in lymphocytic thyroiditis and papillary thyroid cancer.

The controversy on whether or not inflammatory infiltrates in chronic lymphocytic thyroiditis predispose to cancer, has now merged into a debate over the role of the inflammatory infiltrates. The question is how and why some cells become transformed and what factors allow them to spread and in some cases become invasive. Here, we show that the amount of inflammatory mediators such as nitric oxide (NO) and high mobility group Box 1 protein (HMGB1) produced in thyroiditis microenvironment increases in tumors and could be involved in the cellular transformation process. NO and HMGB1 are known to attract macrophages that would promote angiogenesis, matrix remodelling and suppression of an efficient immune response. Inflammatory infiltrates could increase the risk of papillary cancer in patients with autoimmune lymphocytic thyroiditis. Cytokines and soluble inflammatory mediators involved in cancer-related inflammation are not only a target for innovative diagnostic and therapeutic strategies but they also represent a future challenge for oncologists.

Clinical and biological relationship between chronic lymphocytic thyroiditis and papillary thyroid carcinoma.

The association between chronic lymphocytic thyroiditis and papillary thyroid carcinoma has been investigated for several years from different perspectives but with few attempts to design a common frame of reference to understand the complex mutual interactions between the various pathways of inflammatory response and of thyroid tumor induction and progression. This article reviews the current knowledge and research on this topic according to epidemiologic, immunobiologic, pathologic, and biomolecular points of view, highlighting achievements and lack of knowledge. It draws some conclusions and points at possible future directions for research.

Survivin and cyclin D1 are jointly expressed in thyroid papillary carcinoma and microcarcinoma.

In order to define more effective predictive markers for clinical management and prognosis, we evaluated the expression of cyclin D1 and survivin in large papillary thyroid carcinoma (LPTC) and microcarcinoma (PTM). Sixty-seven patients operated for papillary carcinoma (36 of which with PTM) were considered. Immunochemistry for cyclin D1 and survivin was performed in samples from tumor mass and nodal metastases. There were not significant differences between LPTC and PTM as to patients personal data, TNM or MACIS staging, nodal invasion and multifocality, while capsular invasion was significantly more frequent in LPTC. Cyclin D1 and survivin were expressed at a very high rate and almost to the same extent in LPTC and PTM, both in tumoral mass and in nodal metastases. Survivin showed only cytoplasmic expression. Cyclin D1 and survivin over-expression are probably early events in tumorigenesis of thyroid papillary carcinoma but their full role in the process of tumor progression and their clinical value are still to be investigated.

Phenotypic and functional characterization of lymphocytes in autoimmune thyroiditis and in papillary carcinoma.

BACKGROUND: Infiltrates of lymphocytes are found in both autoimmune thyroid disease and papillary cancer and are responsible for thyroid destruction in autoimmune disease. Their role in neoplastic transformation is not yet clear. MATERIALS AND METHODS: Phenotypic studies and the capacity to undergo apoptosis were assessed on peripheral and gland infiltrating lymphocytes from patients with autoimmune thyroiditis and papillary carcinoma. RESULTS: Peripheral lymphocytes in these patients belong to the same phenotype as the infiltrating lymphocytes. A mixed immune response Tc2 and Tc1 is present in thyroid glands of patients with papillary tumors and the capacity to undergo apoptosis in peripheral lymphocytes from both groups of patients increases. CONCLUSION: We suggest that a switch from a Th1 (Tc1) in autoimmune thyroid disease to a Th2 or mixed response in papillary carcinoma patients in peripheral blood may help the early diagnosis of thyroid cancer and could be used in autoimmune thyroid disease patient follow-up.

Clinical value of calcifications in thyroid carcinoma and multinodular goiter.

BACKGROUND: To confirm the predictive value of calcifications in thyroid nodules as a risk factor for malignancy and to detect aspects specific for tumours. MATERIALS AND METHODS: In a set of 196 patients (33 differentiated thyroid carcinoma, 9 follicular adenomas and 154 multinodular goiters with dominant nodule) calcifications were detected by ultrasound scan. RESULTS: Calcifications were significantly more frequent in differentiated thyroid carcinoma (DTC) than in benign diseases (DTC 39.4%, adenoma 11.1%, goiter 20.1%) but their considered characteristics (size, number, position, location in the gland, sonographic features of the nodule) did not show any particular difference between DTC and benign diseases. The frequency of calcifications in our series was higher in older patients (mean age 59.4 +/- 13.7 vs. 52.1 +/- 13.1 in patients without calcifications, p < 0.001) and this could imply that their onset is time-dependent. CONCLUSION: Calcifications can be a useful indicator of enhanced risk, to be considered in the overall diagnostic process.

Death from differentiated thyroid carcinoma: retrospective study of a 40-year investigation.

Differentiated thyroid carcinoma (DTC) usually has a good prognosis, but sometimes the course of the disease results in death. The aim of the present study was to assess the effect of some variables in time to death on fatal cases in our series. A total of 83 patients with DTC who died between 1958 and 1998 from differentiated thyroid cancer were retrospectively analyzed with respect to gender, age at diagnosis, histology, percentage of (131)I uptake by postoperative thyroid remnant, site of tumor growth, and its (131)I uptake, metastases and time to death. Univariate analysis revealed a significantly shorter time to death in local recurrence when comparing local lymph node metastases and distant metastases even if neither show (131)I uptake. Multivariate analysis revealed that age at diagnosis was the most important factor in conditioning the time to death. In conclusion, in those patients who died from DTC an older age at diagnosis and presence of local recurrence influenced the time to death independently of (131)I uptake.