Predictive factors for lymph node involvement in sporadic medullary thyroid microcarcinoma: a systematic review.

OBJECTIVE: The aim of the study was to determine the impact of laboratory and imaging tests in predicting central and lateral neck lymph node/LN involvement and in decision making for surgical extent. MATERIALS AND METHODS: A PubMed, Web of Science and Scopus search was performed according to PRISMA criteria. The relationship between nodule size, diagnostic biomarkers and imaging with LN involvement were evaluated. RESULTS: The available data analysis did not yield clear indications of the relationship between each of these topics and the presence, number, and location of LN involved. There was no conclusive data for the selective indication of central neck dissection in the preoperative diagnosis of microMTC. CONCLUSIONS: There is no justification for less invasive interventions than total thyroidectomy with lymph node dissection.

Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation.

Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1 , all of which contribute to a proliferative phenotype.

Mapping the centers performing endocrine neck surgery in Italy.

BACKGROUND: Quality of care and provider's experience seem to be strictly connected in any field of surgery. Aim of this study is to identify a method to classify the centers on the basis of the number of thyroidectomies and parathyroidectomies performed. METHODS: We listed 666 centers performing endocrine neck surgery in 2015, from the database of the Italian Health Ministry. We performed a descriptive statistic analysis with a dedicated software. We identified the outliers, according to a previous literature review, in those centers performing >1000 and < 10 thyroidectomies, >100 and < 3 parathyroidectomies and we excluded them to our analysis. The remaining centers were grouped in a box-plot. Third quartile, median, procedures performed/3rd quartile value ratio (Standardized Hospitalization Ratio, SHR, superior cut-off), Romamedian/3rd quartile values ratio (inferior cut-off) were calculated. These centers were charted in a bar graph and three zones were identified: "excellence" (SHR>1.1), "SHR", "alert" (between the two cut-offs) and "risk" (under the lower cut-off). RESULTS: 35743 thyroidectomies and 2306 parathyroidectomies were performed in Italy in 2015. After the outliers' exclusion, 407 and 157 centers performing respectively thyroidectomies and parathyroidectomies were analysed. A median value of respectively 37 thyroidectomies and 6 parathyroidectomies, and a 3rd quartile cut-off of respectively 85 and 12 were calculated. Concerning all the 666 centers, we found: 95 excellence centers for thyroidectomy and 33 for parathyroidectomy, respectively 18 and 17 falling into superior cut-off line, 100 and 29 in the alert zone, 453 and 587 in the risk zone. CONCLUSIONS: Our method, according to the literature data, highlighted a number of thyroidectomies and parathyroidectomies performed in low volume centers. Looking for an optimization in health organization, we can consider some measures such as a net of tutorship of the "alert" hospitals by the excellence ones and a discouragement of the "risk" hospitals in performing endocrine neck surgery.

Lack of functional remission in Cushing's syndrome.

INTRODUCTION: Hypercortisolism leads to severe clinical consequences persisting after the onset of remission. These physical sequelae of cortisol exposure are known to profoundly impact the patient's quality of life. As psychological factors may be correlated with this quality of life, our objective was to determine the specific weight of psychological determinants of quality of life in patients in remission from hypercortisolism. PATIENTS AND METHODS: In an observational study, 63 patients with hypercortisolism in remission were asked to complete exhaustive self-administered questionnaires including quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. Multivariate analyses were performed. Psychological variables relevant to the model were: anxiety, depression, self-esteem, body image, and positive thinking dimension of the Brief-COPE. Cortisol deficiency was defined as a potential confounder. RESULTS: The median time since remission was 3 years. Patients had significantly lower quality of life and body satisfaction score than the French population and patients with chronic diseases. Depression significantly impaired all WHOQoL and Cushing QoL domains. A low body satisfaction score significantly impaired social relationships quality of life score. In total, 42.9% of patients still needed working arrangements, 19% had disability or cessation of work. CONCLUSION: Patients in biological remission of hypercortisolism can rarely be considered as functionally cured: this is evidenced by altered quality of life, working arrangements, and chronic depression. A multidisciplinary management of these patients is thus mandatory on a long-term basis.

Long-term esophageal motility changes after thyroidectomy: associations with aerodigestive disorders.

BACKGROUND: Patients undergoing thyroidectomy often complain aerodigestive disorders. In a previous study we showed the associations between voice impairment and proximal acid reflux, swallowing impairment and Upper Esophageal Sphyncter (UES) incoordination and the decrease in UES pressure in thirty-six patients observed before and soon afterwards uncomplicated thyroidectomy. This study investigated the state of post-thyroidectomy esophageal motility changes and its associations with these disorders after 18-24 months. PATIENTS AND METHODS: The thirty-six patients prospectively recruited according to selection criteria (thyroid volume ≤60 ml, benign disease, age 18-65 years, previous neck surgery, thyroiditis, pre- or postoperative vocal cord palsy) underwent voice (VIS) and swallowing (SIS) impairment scores, esophageal manometry and pH monitoring once again. RESULTS: After 18-24 months, both VIS and SIS recovered (respectively: p=0,022; p=0,0001); UES pressure increased (p=0,0001) nearing the preoperative values. The persistence of swallowing complaints were associated with the persistence of esophageal incoordination (p=0,03); the association between voice impairment and proximal acid reflux was confirmed (p<0,001). CONCLUSIONS: Our study confirms that aerodigestive disorders after uncomplicated thyroidectomy, largely transient, are strictly connected with upper esophageal motility changes. In this viewpoint, the innervation of upper aerodigestive anatomical structures (larynx, pharynx, upper esophagus) and its variations should be focused.

The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes.

We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4-Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4-FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis.

Management of adrenal incidentaloma.

Improvements in medical imaging have resulted in the incidental discovery of many silent and unrecognized adrenal tumors. The term "adrenal incidentaloma" (AI) is applied to any adrenal mass≥1cm in its longest axis that is discovered incidentally during abdominal imaging that was not performed to specifically evaluate adrenal pathology. These incidentalomas may be either secretory or non-secretory, benign or malignant. Distinctive characteristics of these lesions must be determined by the clinician to determine appropriate management. Such distinctions are based on laboratory findings and imaging, principally CT with and without contrast injection. Investigations must be carefully chosen to avoid ordering unnecessary and expensive tests for too many patients while, at the same time, avoiding the risk of failing to diagnose a secreting malignant or tumor. These examinations will determine patient care: surgery or surveillance. When simple surveillance is chosen, specific criteria must be met with regard to diagnostic modalities (clinical, imaging, laboratory testing) and its duration.

Minimally invasive video-assisted thyroidectomy: four-year experience of a single team in a General Surgery Unit.

AIM: Minimally invasive video-assisted thyroidectomy (MIVAT) is a surgical technique that has showed increasingly good results, particularly in endocrine surgery centers. The aim of this prospective, non-randomized study was to evaluate feasibility, advantages and critical aspects of MIVAT in a general surgery unit. METHODS: Two hundred twenty-four patients underwent total thyroidectomy for benign thyroid disease from May, 2008 to April, 2011. They were divided into two groups: one underwent conventional thyroidectomy (CT), and the other underwent MIVAT. The inclusion criteria were thyroid volume ≤35 mL and main nodule size ≤35 mm. For each patient, socio-demographic variables, hospitalization data and outcome measures (complication rate, operating time, post-operative pain, observer and patient scar assessment scale [OSAS and PSAS, respectively]) were collected. Multivariate regression analyses were done to assess the principal covariates affecting these outcome measures. RESULTS: There were 125 MIVATs and 99 CTs performed. The two groups were characterized by difference in age (38.4 vs. 50.9 years) and thyroid volume (18.6 vs. 23.3 mL). OSAS/PSAS scores were statistically significant in the MIVAT group (P<0.001 and P<0.001, respectively) even after adjusting for age and thyroid volume. Complication rate was similar in the two groups. CONCLUSION: MIVAT significantly decreased postoperative pain and improved cosmetic results. It can be performed in younger patients and in all cases in which there is a clear indication for the procedure. Its advantages were confirmed in a general surgery unit where correct indications were followed.

KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations.

In natural killer cells, killer immunoglobulin-like receptors (KIRs) loci code for either inhibitory or activating receptors, and according to the number of genes present in each individual, it is possible to identify a high rate of polymorphism in the populations. We performed KIR typing by polymerase chain reaction-sequence-specific oligonucleotide probing in 402 Argentinean Caucasoid and in two Amerindian populations (101 Wichis and 54 Chiriguanos) from the North of Argentina. KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were always present, whereas the frequencies of KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 ranged between 84% and 96%. The frequencies of KIR2DS2, KIR2DL2, KIR2DL5, KIR2DS5, KIR2DS1 and KIR3DS1 ranged between 41% and 62%. The KIR2DS3 with a frequency of 29% in Argentinean Caucasoid population was present at a very low frequency in Amerindian populations. Haplotype segregation studies performed in 10 Wichi families showed the presence of only three haplotypes: A, B5 and B1. The Amerindian populations showed several similarities to Asian but not to Caucasoid populations with regard to the frequency of KIR2DS3, full-length KIR2DS4 gene and KIR2DL4 alleles.

Increased frequencies of activating natural killer receptors are associated with liver injury in individuals who do not eliminate hepatitis C virus.

This study was designed to investigate the role of killer immunoglobulin-like receptor (KIR) genes in the outcome of hepatitis C virus (HCV) infection. In patients who cleared the virus (HCV RNA-) we found a decrease of 2DL2 (P= 0.04), and 2DS2 (P= 0.014) accompanied by an increase of 2DS5 (P= 0.04). Those RNA+ patients with elevated levels of hepatic transaminases (HCV RNA+ elevated alanine aminotransferase) showed an increased frequency of 2DS3 (P= 0.018). Additionally, in cirrhotic patients we found an increased frequency of individuals having two copies of 3DS1 and HLA-Bw4 (P= 0.016). We conclude that higher natural killer cytotoxicity might be associated with a worse progression of the HCV infection.

KIR receptors and HLA-C in the maintenance of pregnancy.

The present study demonstrated that patients who have recurrent spontaneous abortions (RSA) presented a decreased number of killer immunoglobulin-like inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found increased in comparison with controls. Individuals AA will also be homozygous for 2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and therefore a weaker inhibition. The present study might support that in RSA patients, the balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss.