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 to other rare systemic disorders due to presence of melanocytes in other body districts, such as in the 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)

Emerging Therapeutic Approaches for the Most Aggressive Epithelial Thyroid Cancers

The majority of epithelial thyroid carcinomas (TC) have a differentiated (DTC) histotype and include the papillary (PTC) and the follicular (FTC) TC which, ensuing dedifferentiation, generate the aggressive poorly differentiated (PDTC) and anaplastic (ATC) TC. Although derived from the same cell type, each TC shows specific histological features, biological behavior, and degree of differentiation because of different genetic alterations. Total thyroidectomy, followed by adjuvant therapy with 131I, is the treatment of choice for most patients affected by DTC. The prognosis of DTC patients is favorable, with 10‐year survival rate of nearly 90%. However, one third of them face the morbidity of disease recurrence and TC‐related deaths. The worst outcomes are encountered in patients with PDTC and ATC. The latter, in particular, has a mean survival time of few months from the diagnosis, which is not influenced by current anticancer treatments. Following the progress made in the comprehension of the underlying molecular mechanisms deregulated in TC progression, novel therapeutic approaches have come to light. Here, we will attempt to review new targeted therapies, which are currently being exploited in preclinical and clinical studies, with tyrosine kinase inhibitors as well as with emerging inhibitors of mitotic kinases, in PDTC and ATC

Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers

Epithelial thyroid carcinomas (TC) account for more than 90% of all endocrine malignancies and represent one of the most frequent cancers in women. They include the well-differentiated TC (DTC), comprising the papillary (PTC) and follicular (FTC) histotypes, the poorly differentiated (PDTC), and the undifferentiated or anaplastic TC (ATC). Both PDTC and ATC are aggressive human neoplasms with a dire prognosis due to the absence of effective therapies, which makes mandatory the identification of novel therapeutic strategies. Intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) is a common feature of solid tumors and represents a major driving force in thyroid cancer progression, thought to be responsible for the acquisition by malignant cells of novel functional capabilities. Different mitotic kinases, whose expression or function has been found altered in human cancer tissues, are major drivers of thyroid tumor aneuploidy. Among these are the three members of the Aurora family (Aurora-A, Aurora-B and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed with promising antitumor effects in preclinical and clinical studies against different human cancers, including TC. Here, we will focus on the Aurora mitotic functions in normal cells; we shall then describe the main implications of their overexpression in the onset of genetic instability and aneuploidy. We will finally describe the consequences of Aurora kinase inhibition on TC cell growth and tumorigenicity

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 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 down-regulation of CD80 was observed in above all ATC. In addition, the increased expression of CD80 associated to 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 down-regulation, 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

New molecular approaches in the diagnosis and prognosis of thyroid cancer patients

Thyroid nodules are very common in the adult population, but only a minority of them harbor a malignant lesion. Therefore, the first aim in their clinical evaluation is to exclude malignancy. To date, the fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules and cervical lymph nodes (CLN) suspected of metastatic disease. It has to be mentioned, however, that FNAC on thyroid nodules suffers from a major diagnostic limit represented by cellular atypias of indeterminate significance, which require the histological diagnosis. Also the FNAC performed on CLN may be a challenging diagnostic category as CLN could harbor metastases from a multiplicity of extrathyroidal malignancies or be affected by several non-tumoral diseases. In addition, inadequate cellularity obtained from both thyroid nodules or CLN prevents diagnosis in about 20% of specimens. Total thyroidectomy followed by adjuvant therapy with 131I is the treatment of choice for most patients affected by DTC. Although the prognosis of DTC patients is favorable, about 20% of them face the morbidity of disease recurrence and tumor-related deaths. Thus far, the prognosis of these patients still relies on clinic-pathological variables such as patient’s age, tumor size, histology, lymph node or distant metastasis, which are not accurate in predicting the long-term outcome. As a consequence, the identification of new molecular biomarkers strictly related to the risk of DTC relapse is highly needed. In the present review we’ll attempt to summarize the recent characterization of new molecular markers able to ameliorate the diagnosis and prognosis of thyroid cancer patients

Thyroglobulin measurement in the washout of fine needle aspirates for the diagnosis of suspicious cervical lymph nodes

Ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious cervical lymph nodes (CLN) is the gold standard technique for the identification of metastases from differentiated thyroid carcinomas. Thyroglobulin protein (Tgp) assay in the washout of needles employed for FNA biopsies (FNAB) has been reported to refine and support FNAC performances, especially in cases of inadequate sampling or cystic lymph nodes. In the present work, we evaluated the usefulness of routine measurement of Tgp in the FNAB washout of suspicious cervical lymph nodes (CLN), and its ability to increase the FNAC accuracy in the diagnosis of metastatic CLN. A case study of 45 CLN with histological diagnosis from 36 patients was analyzed. Histology showed metastases from papillary thyroid carcinomas (PTC) in 31 CLN, from anaplastic thyroid cancer (ATC) in 3 CLN, from medullary thyroid cancer (MTC) in 4 CLN, and metastases from extrathyroidal malignancies in 5 CLN. Two CLN analyzed were found to be non-neoplastic. The overall accuracy of FNAC was 82.9%, and that of Tgp was 91.1%, not statistically different. However, Tgp determination was found essential in 4 cases of metastatic CLN from DTC with inadequate cytology, and in 1 case in which the FNAC provided a false negative result. We demonstrated that FNAC and Tgp assay show similar diagnostic accuracies, and that Tgp measurement may represent the only available information in case of inadequate lymph node sampling or cystic lymph nodes

Open Surgery for Sportsman's Hernia a Retrospective Study

Sportsman's hernia is a painful syndrome in the inguinal area occurring in patients who play sports at an amatorial or professional level. Pain arises during sport, and sometimes persists after activity, representing an obstacle to sport resumption. A laparoscopic/endoscopic approach is proposed by many authors for treatment of the inguinal wall defect. Aim of this study is to assess the open technique in terms of safety and effectiveness, in order to obtain the benefit of an open treatment in an outpatient management. From October 2017 to July 2019, 34 patients underwent surgery for groin pain syndrome. All cases exhibited a bulging of the inguinal posterior wall. 14 patients were treated with Lichtenstein technique with transversalis fascia plication and placement of a polypropylene mesh fixed with fibrin glue. In 20 cases, a polypropylene mesh was placed in the preperitoneal space. The procedure was performed in day surgery facilities. Early or late postoperative complications did not occur in both groups. All patients returned to sport, in 32 cases with complete pain relief, whereas 2 patients experienced mild residual pain. The average value of return to sport was 34.11 ± 8.44 days. The average value of return to play was 53.82 ± 11.69 days. With regard to postoperative pain, no substantial differences between the two techniques were detected, and good results in terms of the resumption of sport were ensured in both groups. Surgical treatment for sportsman's hernia should be considered only after the failure of conservative treatment. The open technique is safe and allows a rapid postoperative recovery

A Retrospective Case Series in Fournier’s Disease. And Its Emergency Management et Grafting Technique for Penis Coverage

Fournier’s gangrene is a necrotizing soft tissue infection of the genital, perineal, and perirectal areas. A primary isolated involvement of the penis is rare, but it can be elected in some circumstances. •epurpose ofthiscase series isto present the …ndings of our thirteen years’ experience in the reconstruction of the penis in Fournier’s gangrene and our full-thickness grafting technique to cover the penis rod. We retrospectively reviewed patient data who underwent a penis reconstruction following Fournier’s gangrene in 2018. •e data was analyzed to report the estimated percentage of complications, of patients with primary or secondary gangrene of the penis, the number of reinterventions, and …nally the percentage of deaths or recovery. 23 patients underwent reconstruction with our technique of full-thickness skin graft. In all cases, the skin graft was harvested from the upper armwith anarrow shapemark. Nofurther penile revision surgery was required, and neither patient complained about retraction, nor traction, or pain during erection. •e donor site healed without any complications. We believe that the coverage of the penis using our grafting technique is safe, easily reproducible, and demonstrates excellent esthetic and functional results

A Hypothetical New Challenging Use for Indocyanine Green Fluorescence during Laparoscopic Appendectomy: A Mini-Series of Our Experience and Literary Review

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department with an usual range of symptoms for acute appendicitis. The patients were successfully managed by fully LA with the help of a new hypothetical challenging use of ICG-FA