Drawing as a Way of Knowing: How a Mapping Model Assists Preoperative Evaluation of Patients with Thyroid Carcinoma.

Background: Effective pre-surgical planning is crucial for achieving successful outcomes in endocrine surgery: it is essential to provide patients with a personalized plan to minimize operative and postoperative risks. Methods: Preoperative lymph node (LN) mapping is a structured high-resolution ultrasonography examination performed in the presence of two endocrinologists and the operating surgeon before intervention to produce a reliable "anatomical guide". Our aim was to propose a preoperative complete model that is non-invasive, avoids overdiagnosis of thyroid microcarcinomas, and reduces medical expenses. Results: The use of 'preoperative echography mapping' has been shown to be successful, particularly in patients with suspected or confirmed neoplastic malignancy. Regarding prognosis, positive outcomes have been observed both post-surgery and in terms of recurrence rates. We collected data on parameters such as biological sex, age, BMI, and results from cytologic tests performed with needle aspiration, and examined whether these parameters predict tumor malignancy or aggressiveness, calculated using a multivariate analysis (MVA). Conclusions: A standard multidisciplinary approach for evaluating neck lymph nodes pre-operation has proven to be an improved diagnostic and preoperative tool.

Laterocervical lymph node metastases from suspected thyroidal primary site that turned out to be metastases of lung cancer: A case report.

Incidental sonographic discovery of thyroid nodules is an increasingly common event in clinical practice. Less frequently, patients with cytological benign thyroid nodules have suspicious cervical lymph nodes detected by ultrasound examination or by cytological exam. Here, we discuss an intriguing case of cervical lymph node metastasis with a probable thyroid origin in a 65-year-old asymptomatic male smoker. He underwent thyroidectomy and unilateral cervical lymphadenectomy. Despite a negative chest X-ray, the postoperative histological examination revealed that the lymph node metastasis was actually from a lung carcinoma. Metastatic lesions in cervical lymph nodes from non-thyroidal origins must be excluded when evaluating lesions in the region, especially when thyroid nodules subjected to fine needle aspiration biopsy yield negative results, or lymph node cytological evaluations are inconsistent with thyroid cytological findings and sonographic features. Thyroid and lung adenocarcinomas share some epithelial and mesenchymal markers. Thyroglobulin helps differentiate primary thyroid tumors from lung ones, but in cases of poor differentiation, distinguishing metastatic lesions in the thyroid gland can be challenging. Lung cancer (LC) is the leading cause of cancer mortality worldwide, and survival rates have only marginally improved over the last several decades. The ongoing clinical challenge is detecting LC at earlier stages of the disease.

The Size of a Thyroid Nodule with ACR TI-RADS Does Not Provide a Better Prediction of the Nature of the Nodule: A Single-Center Retrospective Real-Life Observational Study.

We investigated if thyroid nodule size has a predictive value of malignancy on a par with composition, echogenicity, shape, margin, and echogenic foci, and what would be the consequence of observing the rule of the American College of Radiology (ACR) to perform a fine-needle aspiration biopsy (FNAB). We conducted a retrospective real-life observational study on 86 patients who underwent surgery after a standardized diagnostic protocol. We divided the TR3, TR4, and TR5 classes into sub-classes according to the size threshold indicating FNAB (a: up to the threshold for no FNAB; b: over the threshold for FNAB suggested). We computed sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for the different sub-classes and Youden's index (Y) for the different possible cutoffs. Each sub-class showed the following PPV (0.67, 0.68, 0.70, 0.78, 0.72), NPV (0.56, 0.54, 0.51, 0.52, 0.59), and Y (0.20, 0.20, 0.22, 0.31, 0.30). In this real-life series, we did not find a significant difference in prediction of malignancy between the sub-categories according to the size threshold. All nodules have a pre-evaluation likelihood of being malignant, and the impact and utility of size thresholds may be less clear than suggested by the ACR TIRADS guidelines in patients undergoing standardized thyroid work up.

Body mass index affects kidney transplant outcomes: A cohort study over 5 years using a steroid sparing protocol.

Background: There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. Patients and methods: Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our center. Patients were stratified according to BMI. Survival outcomes and graft function were analyzed to investigate the effect of donor's and recipient's demographic characteristics. Results: 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21, class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient's BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor's age (p=0.05) and BMI class of the recipient (p=0.002). Conclusions: Obesity did not impact on patient's survival but affected graft function and graft loss.

Low versus high level of physical resemblance in simulation for the acquisition of basic surgical skill: a meta-analysis.

Background: Many studies explored the use of simulation in basic surgical education, with a variety of devices, contexts and outcomes, with sometimes contradictory results. Objectives: The objectives of this meta-analysis were to focus the effect that the level of physical resemblance in a simulation has on the development of basic surgical skill in undergraduate medical students and to provide a foundation for the design and implementation of a simulation, with respect to its effectiveness and alignment with the learning outcomes. Study selection: We searched PubMed and Scopus database for comparative randomised studies between simulations with a different level of resemblance. The result was synthesised as the standardised mean difference, under a random effect model. Findings: We selected 12 out of 2091 retrieved studies, reporting on 373 undergraduate students (mean of subjects 15.54±6.89). The outcomes were the performance of simple skills and the time to complete a task. Two studies reported a scoring system; seven studies reported time for a task; and three studies reported both. The total number of measures included in the meta-analysis was 456 for score and 504 for time. The pooled effect size did not show any significant advantage in a simulation of a high level of physical resemblance over a lower level, both for the scoring system (-0.19, 95% CI -0.44 to 0.06) and for time (-0.14, 95% CI -0.54 to 0.27). Conclusion: Simulations with a low level of physical resemblance showed the same effect as the simulation using a higher level of resemblance on the development of basic surgical skills in undergraduate students.

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.

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.