Genetic and Epigenetic Association of FOXP3 with Papillary Thyroid Cancer Predisposition.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy with an increased female incidence ratio. The specific traits of X chromosome inheritance may be implicated in gender differences of PTC predisposition. The aim of this study was to investigate the association of two X-linked genes, Forkhead Box P3 (FOXP3) and Protein Phosphatase 1 Regulatory Subunit 3F (PPP1R3F), with PTC predisposition and gender disparity. One hundred thirty-six patients with PTC and an equal number of matched healthy volunteers were enrolled in the study. Genotyping for rs3761548 (FOXP3) and rs5953283 (PPP1R3F) was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). The methylation status of FOXP3 was assessed using the combined bisulfite restriction analysis (COBRA) method. The SPSS software was used for statistical analyses. Gender stratification analysis revealed that the CA and AA genotypes and the A allele of FOXP3 rs3761548 variant are associated with PTC predisposition only in females. Moreover, different methylation status was observed up to the promoter locus of FOXP3 between PTC female patients, carrying the CA and CC genotype, and controls. Both revealed associations may explain the higher PTC incidence in females through reducing FOXP3 expression as reported in immune related blood cells.

Sporadic Parathyroid Adenoma: A Pilot Study of Novel Biomarkers in Females.

Background and Objectives: Parathyroid adenoma is a distinct cause of primary hyperparathyroidism, with the vast majority being sporadic ones. Proteomic analysis of parathyroid adenomas has proposed a large number of related proteins. The aim of this study is to evaluate the immunohistochemical staining of ANXA2, MED12, MAPK1 and VDR in parathyroid adenoma tissue. Materials and Methods: Fifty-one parathyroid adenomas were analyzed for ANXA2, MED12, MAPK1 and VDR expressions. Tissue was extracted from formalin-fixed paraffin-embedded parathyroid adenoma specimens; an immunohistochemical study was applied, and the percentage of allocation and intensity were evaluated. Results: ANXA2 stained positively in 60.8% of all cell types, while MED12 had positive staining in 66%. MAPK1 expression was found to be negative in total, although a specific pattern for oxyphil cells was observed, as they stained positive in 17.7%. Finally, VDR staining was positive at 22.8%, based on nuclear staining. Conclusions: These immunohistochemical results could be utilized as biomarkers for the diagnosis of sporadic parathyroid adenoma. It is of great importance that a distinct immunophenotype of nodule-forming cells in a positive adenoma could suggest a specific pattern of adenoma development, as in hereditary patterns.

Rising Glucagon-Like Peptide 1 Concentrations After Parathyroidectomy in Patients With Primary Hyperparathyroidism.

BACKGROUND: Although primary hyperparathyroidism has been associated with insulin resistance, potential optimal effects of parathyroidectomy (PTX) on glucose homeostasis remain controversial. Accordingly, the impact of PTX on glucose-stimulated incretin (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide) secretion has not been evaluated. The aim of this pilot study was to compare glucose-stimulated incretin secretion (GSIS) in patients with asymptomatic primary hyperparathyroidism with normal glucose homeostasis, before and after PTX. METHODS: Fourteen patients were included in the study. Fasting calcium, parathyroid hormone, glucose, insulin, GLP-1, and gastric inhibitory peptide were measured pre- and post-operatively. Homeostasis Model Assessment 2, QUICKI, and Matsuda indexes were used as markers of insulin sensitivity and resistance before and after PTX. Preoperatively, a 75 g oral glucose tolerance test (OGTT) was performed to evaluate the response of glucose, insulin, and GSIS. OGTT measurements were repeated 6 ± 2 wk post-PTX. RESULTS: Patients had a mean age of 52.93 ± 9.96 y, and female-to-male ratio was 12:2. Pre- and post-operatively, a positive correlation between parathyroid hormone and Homeostasis Model Assessment 2 for ß-cell function was evident (r = 0.74, P = 0.002 and r = 0.55, P = 0.04, respectively). After PTX, a significant increase in GSIS for GLP-1 during OGTT was observed (in 60 min: 63.06 ± 44.78 versus 102.64 ± 40.19 pg/mL, P = 0.02; and in 120 min: 71.20 ± 35.90 versus 102.49 ± 40.02 pg/mL, P = 0.03). CONCLUSIONS: The increase of GLP-1 response following oral glucose load after PTX may reflect an initial recovery phase of glucose homeostasis. Long-term studies are required to elucidate the physiological interplay between the normalization of calciotropic axis and the rising GLP-1 concentrations post-PTX.

Do Near-Infrared Intra-Operative Findings Obtained Using Indocyanine Green Correlate with Post-Thyroidectomy Parathyroid Function? the Icgpredict Study.

OBJECTIVE: Postoperative hypoparathyroidism (hypoPT) still remains a significant complication after thyroidectomy. Intra-operative imaging modalities, such as near-infrared fluorescence using indocyanine green (ICG), may assist in identifying and preserving the parathyroid glands (PGs). The purpose of this study was to test the association between the intra-operative ICG staining scoring system and 24-hour postoperative parathyroid hormone (PTH) levels, as well as its capability for intra-operative PG identification. METHODS: This was a prospective study, recruiting patients scheduled for total thyroidectomy by the same surgical team, from December 2018 to April 2019. Intra-operative angiography was performed after infusion of ICG solution (5 mg). Two minutes later, images were acquired using the near-infrared system. RESULTS: Sixty patients fulfilled the eligibility criteria. The percentage of temporary postoperative hypoPT (defined as PTH <14 pg/mL) was 11.66%. No association between intra-operative ICG staining score (expressed as the number of PGs scoring <2 per patient) and 24-hour postoperative PTH (r = 0.011; P = .933) or serum calcium concentrations (r = 0.127; P = .335) was observed. There was also no correlation between the location of PGs scoring ≤2 and postoperative PTH (P = .257) or serum calcium levels (P = .950). Moreover, with regard to secondary endpoint, ICG correctly identified PGs in 98.3% of cases. ICG score was not affected by age, gender, duration of operation, or thyroid gland pathology. No allergic reactions attributed to ICG administration were observed. CONCLUSION: The intra-operative ICG staining scoring system did not predict 24-hour postoperative PTH and serum calcium levels. However, this modality may assist in intra-operative PG identification during a total thyroidectomy.

Comparison Between the Protector™ Laryngeal Mask Airway and the Endotracheal Tube for Minimally Invasive Thyroid and Parathyroid Surgery.

BACKGROUND: Pharyngolaryngeal symptoms are a main concern after neck surgery. The Protector™ LMA is a new supraglottic airway device. The main purpose of this study was to evaluate whether application of the LMA Protector™ causes fewer pharyngolaryngeal symptoms than application of the endotracheal tube after minimally invasive total thyroidectomy and parathyroidectomy. METHODS: This prospective, randomized controlled trial involved one university and one private practice clinic, during the period from January 2017 until November 2017. The patients were randomly allocated to two groups: ETT and LMA. Main outcomes were Numerical Rating Scale scores of postoperative dysphagia, pharyngodynia, and incisional pain. Secondary outcomes were the frequency of rescue analgesia (paracetamol) consumption and emergence cough. Data were recorded in the post-anesthesia care unit and at 1, 6, 12, and 24 h after surgery. RESULTS: Data from 78 patients were included in the final analysis. Pharyngodynia scores were significantly lower in the LMA group, compared with the ETT group, at 1 h, 6 h and 12 h after surgery. Dysphagia and surgical incision pain scores were also significantly lower in the LMA group, compared with the ETT group, at 6 h and 12 h after surgery. The frequency of postoperative paracetamol consumption was significantly increased in the ETT group, compared with the LMA group. Finally, the LMA group had fewer episodes of emergence cough, compared with the ETT group. CONCLUSION: The LMA Protector™ causes fewer pharyngolaryngeal symptoms than the ETT within 6 and 12 h after minimally invasive total thyroidectomy and parathyroidectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03098667.

The outcomes of parathyroid gland autotransplantation during thyroid surgery: a systematic review, meta-analysis and trial sequential analysis.

PURPOSE: Thyroidectomy is the treatment of choice for malignant thyroid diseases as well as for benign conditions who cannot be treated medically. The most common complication following thyroidectomy is hypocalcaemia and hypoparathyroidism that usually results from accidental damage or removal of one or more parathyroid glands. Parathyroid gland autotransplantation has been one of the most common intraoperative strategies applied to tackle this problem. The aim of this study is to assess whether parathyroid auto trasnplantation is associated with a decrease in postoperative hypoparathyroidism following thyroidectomy. METHODS: We conducted a thorough systematic review and meta-analysis of relevant studies published up to February 2024 in MEDLINE, Scopus, Embase and Cochrane Library databases. We compared the incidence of postoperative hypoparathyroidism between the group of patients who underwent autotransplantation and the patients were the parathyroid glands were preserved in situ. A trial sequential analysis was performed subsequently to confirm the findings. RESULTS: Eighteen studies fulfilled all the inclusion criteria and were ultimately included in our study. The total number of patients was 8,182 with 4,029 receiving parathyroid gland autotransplantation. Autotransplantation was associated with a higher incidence of immediate (within 24 h) and transient hypoparathyroidism (RR 1.58, 1.45-1.73, CI 95%, p < 0.00 and RR 1.60, 1.47-1.76, CI 95%, p < 0.001, respectively). However, it did not affect the rate of permanent postoperative hypoparathyroidism (RR 0.85, 0.51-1.41, CI 95%, p = 0.54). The subsequent trial sequential analysis confirmed these findings. CONCLUSION: Parathyroid autotransplantation does not lead to a decrease in the rate of permanent post-thyroidectomy hypoparathyroidism. The most important factor to decrease its incidence remains the accurate identification and preservation of the parathyroid glands intraoperatively.

Thyroidectomy in children and adolescents: a systematic review.

Background: Thyroid surgery in pediatric population is not as common as that in adults, although they share the same indications, techniques and complications. This review aims to evaluate the surgical management of thyroid disease in patients under 18 years old. Methods: We conducted a bibliographic search in the international literature. Data from the identified studies such as demographics, indication for surgery, type of procedure, complications and length of hospital stay were recorded. A retrospective review study of all patients under 18 years old who underwent thyroidectomy was performed. Results: We included 37 retrospective studies and a total of 12,728 patients. Thyroidectomy was more common in female patients and the mean age was approximately 14 years old. The leading indication for surgery was benign thyroid pathology. Due to the surgical treatments' safety and effectiveness in young patients, total and subtotal thyroidectomy, whether for malignancies or benign diseases, is becoming more popular today. The most often occurring complication of pediatric thyroid surgery is hypoparathyroidism. Despite the high likelihood of recurrence of pediatric malignancies, overall survival rates of pediatric thyroid cancer are excellent. Conclusions: Thyroidectomy performed by high-volume thyroid surgeons in children and adolescents is considered an efficient and safe method of treatment of thyroid disease.

Platelet-Rich Therapies in Hernia Repair: A Comprehensive Review of the Impact of Platelet Concentrates on Mesh Integration in Hernia Management.

Mesh-augmented hernia repair is the gold standard in abdominal wall and hiatal/diaphragmatic hernia management and ranks among the most common procedures performed by general surgeons. However, it is associated with a series of drawbacks, including recurrence, mesh infection, and adhesion formation. To address these weaknesses, numerous biomaterials have been investigated for mesh coating. Platelet-rich plasma (PRP) is an autologous agent that promotes tissue healing through numerous cytokines and growth factors. In addition, many reports highlight its contribution to better integration of different types of coated meshes, compared to conventional uncoated meshes. The use of PRP-coated meshes for hernia repair has been reported in the literature, but a review of technical aspects and outcomes is missing. The aim of this comprehensive review is to report the experimental studies investigating the synergistic use of PRP and mesh implants in hernia animal models. A comprehensive literature search was conducted across PubMed/Medline, Web of Science, and Scopus without chronological constraints. In total, fourteen experimental and three clinical studies have been included. Among experimental trials, synthetic, biologic, and composite meshes were used in four, nine, and one study, respectively. In synthetic meshes, PRP-coating leads to increased antioxidant levels and collaged deposition, reduced oxidative stress, and improved inflammatory response, while studies on biological meshes revealed increased neovascularization and tissue integration, reduced inflammation, adhesion severity, and mechanical failure rates. Finally, PRP-coating of composite meshes results in reduced adhesions and improved mechanical strength. Despite the abundance of preclinical data, there is a scarcity of clinical studies, mainly due to the absence of an established protocol regarding PRP preparation and application. To this point in time, PRP has been used as a coating agent for the repair of abdominal and diaphragmatic hernias, as well as for mesh fixation. Clinical application of conclusions drawn from experimental studies may lead to improved results in hernia repair.

Exploring the Link between BMI and Aggressive Histopathological Subtypes in Differentiated Thyroid Carcinoma-Insights from a Multicentre Retrospective Study.

Obesity's role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients (<55 years old) with PTC > 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics.

The Impact of Change Management in the Greek National Health System: A Quantitative Study.

INTRODUCTION:  Serious changes took place in Greece due to the economic crisis of 2008, which led to significant changes in Greece's health sector. The reforms and changes that were made to the National Health System (NHS) aimed to improve it, provide quality services to its users, and adapt it to Greece's new external environment. The aim of this study was to assess the management of these changes by the leadership of the NHS and to examine their effectiveness. MATERIAL AND METHODS: The survey was based on quantitative research methods, using a questionnaire as a research tool. The sample population comprised employees of a tertiary-care public hospital in northern Greece. RESULTS:  We recruited a sample size of 100 participants for the survey. The questionnaire's Cronbach's alpha was equal to 0.724. The overall change management was moderate, and Greece's NHS did not follow a specific change-management model that provided principles facilitating the success of the effort. The most serious problems identified by using the questionnaire were the following: the changes were not structured and clear, the management set unrealistic goals and objectives, the changes to the NHS were made without the appropriate financial support, and there is uncertainty about the future of health care in Greece. CONCLUSION: The present study showed that changes cannot be made randomly; rather, they require careful planning and organization. Further changes, continuous feedback, and development are required to improve the status of Greece's healthcare system.

Visualization of the recurrent laryngeal nerve alone versus intraoperative nerve monitoring in primary thyroidectomy: a framework approach to a missing typology.

Introduction: Surgical studies evaluating a device or technology in comparison to an established surgical technique should accurately report all the important components of the surgical technique in order to reduce the risk of intervention bias. In the debate of visualization of the recurrent laryngeal nerve alone (VONA) versus intraoperative nerve monitoring (IONM) during thyroidectomy, surgical technique plays a key role in both strategies. Our aim was to investigate whether the surgical technique was considered as a risk of intervention bias by relevant meta-analyses and reviews and if steps of surgical intervention were described in their included studies. Methods: We searched PUBMED, CENTRAL-Cochrane library, PROSPERO and GOOGLE for reviews and meta-analyses focusing on the comparison of IONM to VONA in primary open thyroidectomy. Τhen, primary studies were extracted from their reference lists. We developed a typology for surgical technique applied in primary studies and a framework approach for the evaluation of this typology by the meta-analyses and reviews. Results: Twelve meta-analyses, one review (388,252 nerves at risk), and 84 primary studies (128,720 patients) were included. Five meta-analyses considered the absence of typology regarding the surgical technique as a source of intervention bias; 48 primary studies (57.14%) provided information about at least one item of the typology components and only 1 for all of them. Discussion: Surgical technique of thyroidectomy in terms of a typology is underreported in studies and undervalued by meta-analyses comparing VONA to IONM. This missing typology should be reconsidered in the comparative evaluation of these two strategies.

A Pilot Study of the Association VDR Polymorphisms With Primary Hyperparathyroidism.

BACKGROUND/AIM: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder characterized by autonomous parathyroid hormone (PTH) production from one or more parathyroid glands and hypocalcemia. Vitamin D through its receptor is a principal regulator of parathyroid glands function. VDR gene polymorphisms, which affect the expression or structure of VDR protein, may be involved in the genetic pathogenesis of PHPT. The aim of this study was to investigate the role of FokI, ApaI, TaqI, and BsmI VDR gene polymorphisms as genetic predisposing factors for PHPT. PATIENTS AND METHODS: Fifty unrelated patients with sporadic PHPT and an equal number of corresponding ethnicity, sex and age range healthy volunteers were enrolled in the study. Genotyping was performed with polymerase chain reaction and restriction fragment length polymorphism assay. RESULTS: Statistically significant difference was observed in TaqI genotype distribution between PHPT patients and controls, while no association was detected for the other studied polymorphisms. CONCLUSION: TaqI TT and TC genotypes may be associated with PHPT risk in Greek population. Further independent studies are needed to replicate and validate the role of VDR TaqI polymorphism in PHPT predisposition.

Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.

BACKGROUND: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery. METHODS: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual. RESULTS: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample. CONCLUSIONS: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001598471.

Effect of Parathyroidectomy on Left Ventricular Mass Index in Patients With Primary Hyperparathyroidism.

Aim Primary hyperthyroidism (PHPT) is known to affect left ventricular structure and function and may contribute to increased cardiovascular morbidity and mortality. Whether parathyroidectomy (PTX) reverses left ventricular hypertrophy/remodeling among PHPT patients remains controversial. Method In this prospective, single-center study, we enrolled patients with the diagnosis of PHPT who were scheduled for PTX. Patients underwent a complete biochemical workup and an echocardiographic examination at baseline and a six-month follow-up. The primary objective was to compare the left ventricular mass index (LVMI) at baseline and six-month follow-up. Result Eighteen patients (15 female, three male, mean age 58.7 years) were enrolled. PTH and serum calcium returned to normal immediately post-PTX and remained normal at six months. LVMI at baseline was within normal limits and reduced further at the six-month follow-up. The left ventricular ejection fraction was in the normal range before the PTX and remained unchanged during follow-up. Conclusion Curative PTX reduced LVMI further within the normal range at six months in patients with asymptomatic hyperparathyroidism, providing evidence for benefit in an important non-traditional disease manifestation.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Predictive Factors for Mortality and Length of Hospital Stay after Cardiac Surgery.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are widely accepted indices positively correlated with disease severity, progression, and mortality. In this study, we tested whether NLR and PLR could predict mortality and length of hospital stay (LOS) after cardiac surgery. METHODS: NLR and PLR were calculated on days 0, 3, 5, and 7 postoperatively. A ROC curve was generated to assess their prognostic value; multivariate logistic analysis identified independent risk factors for 90-day mortality. RESULTS: Analysis was performed on 179 patients' data, 11 of whom (6.15%) died within 90 days. The discriminatory performance for predicting 90-day mortality was better for NLR7 (AUC = 0.925, 95% CI:0.865-0.984) with the optimal cut-off point being 7.10. NLR5 and PLR3 also exhibited a significant strong discriminative performance. Similarly, a significant discriminative performance was prominent for PLR3, NLR5, and NLR7 with respect to LOS. Moreover, NLR7 (OR: 2.143, 95% CI: 1.076-4.267, p = 0.030) and ICU LOS (OR:1.361, 95% CI: 1.045-1.774, p = 0.022) were significant independent risk factors for 90-day mortality. CONCLUSIONS: NLR and PLR are efficient predictive factors for 90-day mortality and LOS in cardiac surgery patients. Owing to the simplicity of determining NLR and PLR, their postoperative monitoring may offer a reliable predictor of patients' outcomes in terms of LOS and mortality.

Buried bumper syndrome: A critical analysis of endoscopic release techniques.

Buried bumper syndrome (BBS) is the situation in which the internal bumper of the gastrostomy tube, due to prolonged compression of the tissues between the external and the internal bumper, migrates from the gastric lumen into the gastric wall or further, into the tract outside the gastric lumen, ending up anywhere between the stomach mucosa and the surface of the skin. This restricts liquid food from entering the stomach, since the internal opening is obstructed by gastric mucosal overgrowth. We performed a comprehensive search of the PubMed literature to retrieve all the case-reports and case-series referring to BBS and its management, after which we focused on the endoscopic techniques for releasing the internal bumper to re-establish the functionality of the tube. From the "push" and the "push and pull T" techniques to the most sophisticated-using high tech instruments, all 10 published techniques have been critically analysed and the pros and cons presented, in an effort to optimize the criteria of choice based on maximum efficacy and safety.

Gastrointestinal Stromal Tumors: Our Ten-Year Experience of a Single-Center Tertiary Hospital.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. They have variable clinical presentation, prognosis, and molecular characteristics. Here, we present the results of our retrospective study including patients operated on for GIST during the last decade. METHODS: All the patients who underwent GIST resection during the decade 2008-2018 were included in the study. The diagnosis was based on the pathology report. All the data were collected and analyzed statistically using the Statistical Package for Social Science v25.0. Finally, after having applied the proper search terms, a comprehensive review of articles published in the Medline database was held. RESULTS: Thirty-two patients (sixteen women) were included in the study with a mean age of 69.6 years old (SD = 13.9). Twenty-one patients had a GIST in the stomach, eight in the small intestine, and three had an extra GIST. Of the 29 patients contacted, 21 were alive with a mean survival time of 74.3 months (SD = 49.6 months, min: 3.0 months, max: 161.0 months), whereas eight patients passed away. Finally, 13 patients were treated with tyrosine kinase inhibitors (TKIs) of whom only one died, while 9 patients passed away from those treated with surgery alone (p = 0.031). CONCLUSIONS: Our results were in concordance with the existing data in the literature. GISTs require patient-based therapeutical management depending on the histology of the tumors. Gastric tumors present a better prognosis than those localized in the intestine, while the use of TKIs has led to an improvement in patient survival rate.

The Implication of X-Linked Genetic Polymorphisms in Susceptibility and Sexual Dimorphism of Cancer.

The X-chromosome is implicated in cancer development through various mechanisms, including X-inactivation defects, loss of heterozygosity, and germline and somatic alterations of X-linked genes. Sex is a key factor which influences cancer susceptibility as many cancer types show sexual dimorphism in their incidence. The aim of this review was to summarize the germline genetic polymorphisms lying on the X-chromosome that have been associated with cancer susceptibility and to evaluate their possible implication in cancer-related sexual dimorphism. PubMed and Web of Science were searched using the terms "X-chromosome", "polymorphism" and "cancer". The literature review revealed 39 articles reporting 33 genetic variants in 22 X-linked genes as being associated with cancer risk. Most of these genes interact with each other in a direct or indirect way, as GeneMANIA software revealed, demonstrating the complication of the mechanisms through which they are involved in tumorigenesis. Polymorphisms in eight genes [androgen receptor (AR), fibroblast growth factor 13 (FGF13), forkhead box P3 (FOXP3), L1 cell adhesion molecule (L1CAM), nudix hydrolase 11 (NUDT11), Shroom family member 2 (SHROOM2), transcription elongation factor A-like 7 (TCEAL7) and TIMP metallopeptidase inhibitor 1 (TIMP1)] are reported to have a sex-specific association with cancer susceptibility, which might explain the sexual dimorphism of certain cancer types. All of the above eight mentioned genes, with the exception of L1CAM, exhibit differences in their expression pattern between breast tumor (sex-specific)/thyroid tumor (sex-influenced) vs. normal tissues according to our analysis using GENT2 software. Additionally, differences in breast or thyroid tumor compared with normal tissues were also observed in five genes analyzed with GENT2 software that were previously related to sex-influenced cancer according to literature. Finally, the present review points out the need for the development of appropriate free and user-friendly statistical software in order to reduce bias/errors in statistical analyses and overcome researchers' reluctance to include X-chromosome variants in their genetic-association studies.