In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines.

Increased expression of the urokinase-type plasminogen activator (uPA) system is associated with tumor invasion, neo-angiogenesis, and metastatic spread, and has been shown to positively correlate with a poor prognosis in several cancer types, including thyroid carcinomas. In recent years, several uPA inhibitors were found to have anticancer effects in preclinical studies and in some phase II clinical trials, which prompted us to evaluate uPA as a potential therapeutic target for the treatment of patients affected by the most aggressive form of thyroid cancer, the anaplastic thyroid carcinoma (ATC). In this study, we evaluated the in vitro and in vivo effects of WX-340, a highly specific and selective uPA inhibitor, on two ATC-derived cell lines, CAL-62 and BHT-101. The results obtained indicated that WX-340 was able to reduce cell adhesion and invasiveness in a dose-dependent manner in both cell lines. In addition, WX-340 increased uPA receptor (uPAR) protein levels without affecting its plasma membrane concentration. However, this compound was unable to significantly reduce ATC growth in a xenograft model, indicating that uPA inhibition alone may not have the expected therapeutic effects.

PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications.

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

Thyroid diseases and skin autoimmunity.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Nodular thyroid disease in the elderly: novel molecular approaches for the diagnosis of malignancy.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

Endoscopic mucosal resection in elderly patients.

BACKGROUND: Endoscopic mucosal resection (EMR) of early superficial colorectal carcinomas is nowadays accepted as the gold standard treatment for this type of neoplasia. AIM: This study aims to evaluate the efficacy and safety of mucosectomy in elderly patients considering the predictive value of submucosal infiltration. METHODS: A retrospective study of all patients referred for EMR of sessile colorectal polyps classified IIa by the Paris classification between April 2013 and April 2015. A total of 50 patients (30 males (60 %); age range = 44-86; mean age = 67.7) were enrolled. Patients were divided in two groups considering 65 years as cutoff to individuate the elderly patients. RESULTS: EMR was performed in 53 lesions: 39 were performed en bloc and 14 by piecemeal technique. 30 % of lesions were in the rectum; 11 % in the sigmoid colon; 15 % in the descending colon; 6 % in the transverse colon; 24 % in the ascendant colon; and 14 % in the cecum. The mean size of the resected specimens was 20 mm (range 8-80 mm). The rate of complete resection was 79.2 %, incomplete 13.2 %, not estimable 7 %. Ten patients underwent surgery because of an incomplete resection and/or histological evaluation. CONCLUSIONS: Colon EMR is safe and effective in elderly patients. Endoscopy is still helped in the correct indication for surgery in high-risk surgical patients.

Total fistulectomy, sphincteroplasty and closure of the residual cavity for trans-sphincteric perianal fistula in the elderly patient.

BACKGROUND: Perianal fistula is a complex and frequent disease. At present, no treatment nor technique has shown an absolute superiority in terms of efficacy and recurrence rate. The technique has to be chosen considering the balance between faecal continence preservation and disease eradication. Rarely concomitant perianal abscess and fistula are treated at the same time, and often time to complete recovery is long. AIMS: The aim of this study was to evaluate the possibility of treating the abscess and the fistula tract in one procedure with total fistulectomy, sphincteroplasty and an almost complete closure of the residual cavity, thus reducing the healing time in older patients. METHODS: A non-randomized single-centre series of 86 patients from 2007 to 2012 with low-medium trans-sphincteric perianal fistula (< 30% of external sphincter involvement) with or without synchronous perianal abscess were treated with total fistulectomy, sphincteroplasty and closure of the residual cavity technique. RESULTS: Success rate was 97.7% with a healing time of 4 weeks; overall morbidity was 16.2%; recurrence rate was 2.3%; no major alterations of continence were observed. DISCUSSION: Fistulectomy, sphincteroplasty and closure of the residual cavity are associated with a low rate of recurrence and good faecal continence preservation in older patients. This technique can be safely used even with a concomitant perianal abscess, with reduction in healing time and in the number of surgical procedures needed. CONCLUSIONS: Total fistulectomy with sphincteroplasty and partial closure of the residual cavity, as described, is a safe procedure but has to be performed by dedicated colorectal surgeons.

Prevalence of breast cancer in thyroid diseases: results of a cross-sectional study of 3,921 patients.

Results from national cancer registries reveal an association of thyroid cancers with extra-thyroidal malignancies. In this study, we evaluated the prevalence of breast cancer (BC) in women affected by both benign and malignant thyroid diseases (TD) in comparison to the general population. To this end, 3,921 female patients from central and southern regions of Italy were evaluated. Age-matched analysis of the prevalence of BC was carried out after dividing the patients into three diagnostic categories: (1) 1,149 patients with non-nodular TD; (2) 2350 patients with nodular TD; (3) 422 patients affected by differentiated thyroid cancers. Furthermore, the patients were grouped according to the absence (2,344 patients) or presence (1,453 patients) of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) or anti-TSH receptor auto-antibodies (124 patients). BC prevalence in TD patients as a whole was significantly higher compared to the general population, with an odds ratio (OR) of 3.33. Age-matched analysis showed that the risk of a BC in TD patients was higher in younger patients (age 0-44 years), with an OR of 15.24, which decreased with increasing age. Patients without thyroid auto-antibodies showed a higher OR for BC (p = 0.0005) than TD patients with TgAb and/or TPOAb. The results demonstrate that women affected by either benign or malignant thyroid disease have a significantly greater risk of BC, which is higher at a younger age. Furthermore, thyroid auto-antibodies appear to be protective against BC. These findings may contribute to the identification of common genetic and environmental factors underlying this disease association.

In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval.

CONTEXT: It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease-free interval (DFI). OBJECTIVES: To investigate the effects of BRAF(V600E) on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAF(V600E) alone or in combination with uPA and uPAR. DESIGN/SETTING/PATIENTS/INTERVENTION: The case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow-up was available for 75 patients. MAIN OUTCOME MEASURES: The BRAF(V600E) mutation was analysed by sequencing and mutant allele-specific PCR amplification; uPA and uPAR expression by quantitative RT-PCR. RESULTS: BRAF(V600E) was found in 44 of the 91 patients and associated with older age, but not with high-risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9·51 ± 1·30 and 4·64 ± 0·44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAF(V600E) -positive patients. In vitro induction of BRAF(V600E) in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. Kaplan-Meier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAF(V600E) was not. CONCLUSION: In PTC, BRAF(V600E) induces uPA and uPAR expression. The latter, but not BRAF(V600E) , associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision-making in patients with PTC.

Should the host reaction to anisakiasis influence the treatment? Different clinical presentations in two cases.

Gastrointestinal anisakiasis is a parasitic infection occurring in people that consume raw or inadequately cooked fish or squid. It is frequently characterized by severe epigastric pain, nausea and vomiting caused by the penetration of the larvae into the gastric wall. Acute gastric anisakiasis with severe chest discomfort is rarely reported in Italy. On the other hand, gastro-allergic anisakiasis with rash, urticaria and isolated angioedema or anaphylaxis is a clinical entity that has been described only recently. Also, if patients usually develop symptoms within 12 hours after raw seafood ingestion, not always endoscopic exploration can promptly identify the Anisakis larvae. Moreover, some authors consider the prevailing allergic reaction as a natural and effective defense against the parasitic attack. We report two cases of peculiar manifestations of anisakiasis in both acute and chronic forms (severe chest discomfort and anaphylactoid reaction).

Papillary Thyroid Cancer Prognosis: An Evolving Field.

Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients' staging and being able to choose a clinical approach tailored on single patient's needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.

Expression and Clinical Utility of Transcription Factors Involved in Epithelial-Mesenchymal Transition during Thyroid Cancer Progression.

The transcription factors involved in epithelial-mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients' clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

Meta-analysis of randomized trials on the efficacy of vascular closure devices after diagnostic angiography and angioplasty.

BACKGROUND: The aim of this meta-analysis was to evaluate the safety and efficacy of vascular closure devices (VCDs). METHODS: This meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews. RESULTS: The literature search yielded 31 prospective, randomized studies including 7,528 patients who were randomized to VCDs or manual/mechanical compression after diagnostic angiography and/or endovascular procedures. Most of these studies have excluded patients at high risk of puncture site complications. Meta-analysis showed similar results in the study groups in terms of groin hematoma, bleeding, pseudoaneurysm, and blood transfusion. Lower limb ischemia and other arterial ischemic complications (0.3% vs 0%, P = .07) as well as need of surgery for vascular complications (0.7% vs 0.4%, P = .10) were somewhat more frequent with arterial puncture closure devices. The incidence of groin infection was significantly more frequent with VCDs (0.6% vs 0.2%, P = .02). The use of VCD was uniformly associated with a significantly shorter time to hemostasis. Such differences where more evident in patients undergoing percutaneous coronary intervention, whereas these methods were associated with similar rates of adverse events among patients undergoing diagnostic coronary angiography. CONCLUSIONS: The use of VCDs is associated with a significantly shorter time to hemostasis and thus may shorten recovery. However, the use of VCDs is associated with a somewhat increased risk of infection, lower limb ischemia/arterial stenosis/device entrapment in the artery, and need of vascular surgery for arterial complications. Further studies are needed to get more conclusive results, particularly in patients at high risk of femoral puncture-related complications.

Evaluation of Clinicopathological and Molecular Parameters on Disease Recurrence of Papillary Thyroid Cancer Patient: A Retrospective Observational Study.

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan-Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model.

CTLA-4 and PD-1 Ligand Gene Expression in Epithelial Thyroid Cancers.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80, and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

Iodine deficiency in pregnancy: Still a health issue for the women of Cassino city, Italy.

OBJECTIVE: The World Health Organization, the United Nations Children's Fund, and the International Council for the Control of Iodine Deficiency Disorders recommend a median urinary iodine concentration (UIC) in pregnant women between 150 µg/L and 249 µg/L. In the present study, we evaluated whether in the urban area of Cassino (central Italy), after a national salt iodination program (30 mg/kg) was introduced in 2005, the increased demand of iodine during pregnancy was satisfied. METHODS: Between January 2016 and April 2017, 99 pregnant women were enrolled to evaluate UIC in spot urine samples, serum level of thyrotropin, free thyroxine, antithyroglobulin and antithyroperoxidase autoantibodies, and thyroid volume by ultrasonography. Eighty clinically healthy non-pregnant women were evaluated as controls. RESULTS: The median UIC was of 97.7 µg/L and 110.3 µg/L, respectively, in control and pregnant women. A significant increase (P < 0.001) of median thyroid volume was found in pregnant women, relative to control women, being, respectively, 10.4 mL (range 3.68-19.49 mL) and 7.16 mL (range 2.57-14.00 mL). A positive correlation was found between thyroid volume and anthropometric parameters, and an inverse correlation was identified between free thyroxine serum levels and anthropometric parameters. CONCLUSIONS: This observational study found that the majority of pregnant women and their fetuses appear not to be protected from the detrimental consequences of iodine deficiency. Therefore, the identification of new strategies to increase the knowledge and awareness of the general population regarding the beneficial effects of iodine supplementation during pregnancy is highly required.

New perspectives in the diagnosis of thyroid follicular lesions.

Thyroid nodules are very common, affecting 19%-67% of the adult population. However, about 10% of them harbor a malignant lesion. Consequently, the first aim in their clinical evaluation is to exclude malignancy. Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of indeterminate significance, which require surgical excision and histological examination to differentiate benign from malignant lesions. Histology reports show that approximately 80% of these patients harbor a benign lesion. Therefore, in order to reduce unnecessary thyroidectomy, over the last years, the cytological classification of thyroid nodules has been revised and a number of new instrumental and molecular approaches have been proposed. In the present article, we will attempt to summarize the most recent cytological, molecular and echographic strategies to enhance the diagnostic accuracy of preoperative thyroid follicular lesions. In particular, we will discuss the new cytological classifications from the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA-RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC 2014. We will review molecular tests evaluated to ameliorate follicular lesion diagnosis as well as the clinical utility of the new echographic Thyroid Imaging Reporting and Data System (TI-RADS) score.

Vitiligo and Autoimmune Thyroid Disorders.

Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves' disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).

Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules.

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p = 0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p = 0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Deregulated expression of VHL mRNA variants in papillary thyroid cancer.

Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences.

The sentinel lymph node in papillary cancer of the thyroid including histological subtype.

BACKGROUND: The aim of this work was to reveal through sentinel node study the intraoperative presence of preoperatively undetected pathological lymph nodes. MATERIALS AND METHODS: At the Surgical Science Department of La Sapienza University of Rome The Authors studied from January 2003 to June 2004 18 patients with papillary carcinoma of the thyroid, who presented no clinical evidence of lymph node metastasis; they performed a total thyroidectomy in all cases, removing and histologically examining all lymph nodes of the upper anterior mediastinum. Where negative they were then subjected to immunohistochemical analysis with Pan Cytokeratin. RESULTS: The method was positive in 10 patients: 2 pure papillary carcinomas, 1 papillary carcinoma with poorly differentiated areas, 1 tall cell papillary carcinoma, 5 sclerosing carcinoma and 1 follicular variant papillary carcinoma; and negative in 8:5 pure papillary carcinomas, 2 sclerosing carcinoma and 1 case of follicular variant papillary carcinoma. Lymph node micrometastasis was found in 2 cases through study with Pan Cytokeratin on final histological examination. CONCLUSIONS: Analysis of the Authors' preliminary data shows that sentinel lymph node detection has 83.3% sensitivity and 100% specificity for Upper Anterior Mediastinum lymph nodes. The Authors can propose two main applications: select for dissection only patients with a positive sentinel node and reduce the number of cases to be subjected to postoperative treatment with iodine ablation, in patients with "low risk" thyroid tumours and negative sentinel nodes.