Comparison of endoscopic versus focused parathyroidectomy in surgical management of single-gland primary hyperparathyroidism: a randomized clinical trial.

BACKGROUND: Over recent years, various advanced minimally invasive techniques have been developed for parathyroidectomy, and there was a universal acceptance of these less invasive procedures by surgeons. This study is designed to compare overall outcomes between endoscopic versus focused, single gland parathyroidectomy using intraoperative rapid parathyroid hormone (ioPTH) changes under general anesthesia in primary hyperparathyroidism (PHPT) patients. METHOD: In this randomized clinical trial, 96 patients diagnosed with PHPT were randomly assigned into two groups endoscopic and focused parathyroidectomy. Baseline clinical and demographical data were collected along with perioperative features. The success rate was evaluated based on ioPTH changes. RESULTS: The ioPTH levels after five minutes in the endoscopic group were significantly lower than the focused group (P = 0.005). The success rate for endoscopic and the focused method was 95.3% and 77.1% during the first five minutes (P = 0.013) and 100% in both groups after ten minutes. A decrease in parathyroid hormone levels was significant in each group but not between each other. Postoperative calcium levels were significantly lower in the focused method (P = 0.042). The focused group also had a significantly shorter operation time than the endoscopic group (P < 0.001). Patient satisfaction with cosmetic outcome was significantly higher in the endoscopic group compared to the focused group. CONCLUSION: The endoscopic technique was superior to the unilateral focused neck exploration parathyroidectomy in the management of single-gland PHPT. Influencing aspects included higher postoperative calcium levels, more rapid success achievement, and satisfactory cosmetic outcomes in the endoscopic group. However, patient selection and accurate adenoma localization are vital in this method.

Plasma metabolites analysis of patients with papillary thyroid cancer: A preliminary untargeted 1H NMR-based metabolomics.

Metabolomics plays a crucial role in identifying molecular biomarkers that can differentiate pathological conditions. In the case of thyroid cancer, it is essential to accurately diagnose malignancy from benignity to avoid unnecessary surgeries. The objective of this research was to apply untargeted NMR-based metabolomics in order to identify metabolic biomarkers that can distinguish between plasma samples of patients with papillary thyroid cancer (PTC) and multinodular goiter (MNG), as well as PTC and healthy individuals. The study included a cohort of 55 patients who were divided into three groups: PTC (n=20), MNG (n=16), and healthy (n=19). Plasma samples were collected from all participants and subjected to 1H NMR spectroscopy. Differential metabolites were identified using chemometric pattern recognition algorithms. The obtained metabolic profile had the potential to differentiate PTC from healthy plasma, but not from MNG. In patients diagnosed with PTC, a total of 18 compounds were discovered, revealing elevated levels of leucine, lysine, and 4-acetamidobutyric acid, while acetate, proline, acetoacetate, 3-hydroxybutyrate, glutamate, pyruvate, cystine, glutathione, asparagine, ethanolamine, histidine, tyrosine, myo-inositol, and glycerol along with a lipid compound were found to be lower in comparison to those of healthy individuals. According to the area under the curve (AUC) of the receiver operating characteristic curve, this particular profile exhibited an impressive capability of 85% to discern PTC from healthy subjects (AUC=0.853, sensitivity=78.95, specificity=84.21). The utilization of the 1H NMR-based metabolomics approach revealed considerable promise in the identification of PTC from healthy plasma specimens. The modifications noticed in the plasma metabolites have the potential to act as practical biomarkers that are non-invasive and could suggest transformations in the metabolic profile of thyroid tumors.

Investigating the effectiveness of intraoperative rapid parathyroid hormone assay in parathyroidectomy surgery in patients with secondary hyperparathyroidism.

INTRODUCTION: The use of Rapid Intraoperative parathyroid hormone (Io-PTH) assay during surgery in the management of parathyroid tissue in cases of primary hyperparathyroidism has been proven to be effective, while its utilization in secondary hyperparathyroidism (SHPT) has been rarely reported. In the present study, we aim to demonstrate the application of rapid Io-PTH assay in patients with SHPT following chronic kidney disease undergoing parathyroidectomy surgery. METHOD: In this prospective study, five blood samples were taken from patients undergoing parathyroidectomy and upper thymectomy. Among the samples, two were pre-excision, including prior to the first incision, after exploration, and before parathyroids resection. Two additional samples were taken 10 and 20 min after the excision of the parathyroid glands. Another sample was collected twenty-four hours after the operation. Serum Calcium levels and PTH levels were evaluated and analyzed. RESULTS: We successfully managed SHPT in all 36 patients in our study. The patients included 24 males (66.7%) with a mean age of 49.97 ± 14.92. The mean PTH decreased significantly at 10 min, 20 min, one day, and six months after surgery (P < 0.001). The highest reduction occurred 10 min after removal of the parathyroid glands so the mean PTH compared to time zero was reduced from 1737 to 439, and in 100% of cases, more than 50% reduction was seen in PTH. CONCLUSION: A 60% or more reduction in PTH Rapid at 10 min after parathyroidectomy has an accuracy of 94.4% and a positive predictive value of 100%. Thus, if the PTH level does not decrease by more than 60% at 10 min or more than 80% at 20 min, tissue exploration is continued with the aim of finding the ectopic parathyroid gland.

The evaluation of locoregional tumoral involvement in the cooccurrence of hashimoto thyroiditis with papillary thyroid cancer: a case controlled study.

BACKGROUND: Papillary thyroid carcinoma PTC is the most prevalent of all thyroid carcinomas. On the other hand, Hashimoto's thyroiditis (HT), as part of the spectrum of autoimmune thyroid diseases, is a major cause of thyroid hypofunction worldwide. Several studies have aimed to indicate a possible correlation between PTC and HT over the years. This study aims to investigate the correlation between HT disease and PTC tumor invasion rate. METHOD: In the present cross-sectional study, PTC patients with HT were selected among patients referred to the surgical ward of Shariati hospital from 2016 to 2019 and compared in terms of tumor invasion and central LN dissection. Also, a similar group of PTC patients without HT undergoing total thyroidectomy was selected for comparison. The tumor invasion rate was assessed based on invasion indices obtained from postoperative permanent pathology specimens. These indices included tumor type and size, number of involved LNs, lymphovascular involvement, perineural involvement, thyroid capsule involvement, multifocal or unifocal tumor, extrathyroidal proliferation, marginal status, and necrosis. Data were obtained and compared in the two groups with SPSS version 22.0 software. RESULTS: Based on the postoperative pathology reports, 50 (56.2%) PTC patients with Hashimoto thyroiditis were compared against 39 PTC patients without Hashimoto thyroiditis. No significant difference was found between the two groups regarding tumor invasion factors such as multifocality, lymphovascular invasion, marginal invasion, extrathyroidal invasion, capsular invasion, and necrosis. CONCLUSION: HT could not be mentioned as an aggravating factor of PTC invasion based on the invasion factors evaluated in pathology specimens.

Evaluation of the role of prophylactic bilateral central neck lymph node dissection in patients with papillary thyroid carcinoma: a case controlled study.

Thyroid cancer is the most common malignancy in the endocrine system. Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer. There are considerable discrepancies regarding the role and extent of prophylactic central lymph node dissection (PCLND) for patients with PTC. Our primary goal was the evaluation of CLN involvement based on the tumor features and staging on the eight version of the American Joint Committee on Cancer and also the TNM method. Our secondary aim was to evaluate the features of the CLNs with tumoral features and also features associated with the development of transient hypoparathyroidism. This prospective case-controlled study was performed among PTC patients. Total thyroidectomy and bilateral dissection of the CLNs of the central compartment of the neck was performed, and samples were sent for pathological evaluation. CLN involvement, tumoral features and transient hypoparathyroidism were cross-evaluated and analyzed with SPSS version 26.0. In this study, out of 61 patients, 11 (18%) were male, the average age was 37.3 ± 13.7 years, based on AJCC staging, 53 (86.9%) were stage I and 8 (13.1%) were stage II, and based on TNM staging, 39 patients (66.1%) were T1, including 13 (22.0%) T1a and 26 (44.1%) T1b, 15 patients (25.4%) were T2, and five patients (8.5%) were T3. Based on permanent pathology evaluation, the majority of patients (n = 48; 78.7%) had CLN involvement. None of the preoperative and tumor features had a significant association with CLN involvement. 75% of stage I and 100% of stage two cases, while 76.9% of T1, 86.7% of T2, and 80.0% of T3 cases had CLN involvement. There was no significant association between the involvement of CLN and the AJCC staging (P = 0.184) or TNM staging (P = 0.875). The involved to dissected CLN ratio was significantly higher in stage II patients compared to stage I (72.5 vs. 34.8%; P = 0.006), and also with higher T staging (0.009). There was a statistically significant association between the larger CLN size and older patients' age, higher postoperative thyroglobulin levels, and smaller tumor size. Higher postoperative thyroglobulin level was significantly associated with larger tumors size and thyroid capsule invasion. Also, 26 (44.8%) of patients developed transient hypoparathyroidism, which was significantly associated with vascular invasion (P = 0.048), bilateral location of tumor (P = 0.048) or on the right side (0.005), and larger size of the tumor (P = 0.016). Tumor features and staging were not associated with CLN involvement features. Therefore, full extent PCLND should be carried out to avoid reoperation or metastasis in PTC patients.

The effect of thymectomy during central neck dissection in papillary thyroid carcinoma: a case-controlled study.

Central lymph-node dissection (CND) as part of total thyroidectomy is recommended in the treatment of papillary thyroid cancer. CND with thymus resection for achieving more oncological clearance is suggested in guidelines, but the benefits of this technique are still unclear due to the risk of parathyroid glands injury and postoperative hypocalcemia. The aim of this study is to evaluate the risk and benefits of thymectomy in CND with total thyroidectomy. We retrospectively reviewed the records of 188 patients with total thyroidectomy and CND. Participants were divided into 110 patients with CND and thymus resection and 78 patients with thymus preservation. Oncological completeness was evaluated by measuring the postoperative thyroglobulin and hypocalcemia as a postoperative complication was measured by blood calcium level. Based on our findings, patients who underwent thymus resection had a higher incidence of hypocalcemia compared to patients with thymus preservation (56.4% vs. 39.2%; P = 0.027), but there was no significant difference in thyroglobulin levels between these two groups. (P = 0.115 and 0.185, respectively) The proportion of involved to total resected lymph nodes in our study was 28%, which did not statistically differ among the thymus groups. Routine thymus resection during the CND and total thyroidectomy is not recommended because of more postoperative hypocalcemia occurrence and minimal oncological benefit in PTC treatment.

Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules.

BACKGROUND: Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules. METHODS: Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n=30), multinodular goiter (MNG; n=30), and healthy subjects (n=22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups. RESULTS: Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90±1.35, MNG: 4.89±1.37, and healthy: 3.13±1.42) and MT6-MMP (PTC: 8.29±2.50, MNG: 7.34±2.09, and healthy:5.01±2.13) in thyroid nodules by comparison with healthy subjects (P<0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P>0.05). Increased plasma levels of MT4-MMP (odds ratio=2.48; 95% CI: 1.46-4.19; P=0.001) or MT6-MMP (odds ratio=1.81; 95% CI: 1.29-2.53; P=0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r=0.766**, P=0.000; MNG: r=0.856**, P=0.000; healthy r=0.947**, P=0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value>4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity. CONCLUSION: Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings.

Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAFV600E mutation as biomarkers for papillary thyroid carcinoma.

Circulating cell-free DNA (cfDNA) has been considered as a diagnostic source to track genetic and epigenetic alterations in cancer. We aimed to study mutation in addition to the methylation status in the promoter regions of RASSF1 and SLC5A8 genes in tissues and circulating free DNA samples of patients affected with papillary thyroid carcinoma (PTC) and thyroid nodules as controls. BRAFV600E mutation was studied by ARMS-scorpion real-time polymerase chain reaction method in 57 PTC and 45 thyroid nodule cases. Methylation status of RASSF1 and SLC5A8 promoter regions was analyzed by methylation-specific high-resolution melting curve analysis. BRAFV600E mutation was found in 39 (68.4%) out of 57 PTC tissue samples, while in 33 (49.1%) cases of cfDNA, this mutation was detected. The frequency of BRAFV600E mutation in cfDNA was significantly different between metastatic and nonmetastatic PTC cases (22 of 33 PTC cases vs. 5 of 34 thyroid nodule samples). Methylation levels of three promoter regions of SLC5A8 and proximal promoter region of RASSF1 was significantly different between PTC and thyroid nodule cases in both cfDNA and tissue DNA. In addition, the methylation status of these two genes in tissue DNA was reflected in methylation status observed in cfDNA. This study confirmed that BRAFV600E mutation is better for discrimination between papillary thyroid carcinoma and thyroid nodules. On the other hand, hypermethylation in the more proximal promoter regions to RASSF1 and SLC5A8 genes showed higher sensitivity and more acceptable specificity for this discrimination.

Relationship Between Preoperative 25-Hydroxy Vitamin D and Surgical Site Infection.

BACKGROUND: Surgical site infection (SSI) is one of the most important and costly complications of surgical operations. Vitamin D antimicrobial and wound healing effects have been recently shown in animal models and in laboratory settings. Furthermore, potential effects of vitamin D in mitigating nosocomial infections and SSIs have been examined at a limited scale. To our knowledge, no comprehensive study has been performed to show the relationship between preoperative level of vitamin D and incidence of SSI. The present study was designed and implemented to investigate this relationship. MATERIALS AND METHODS: We performed a prospective cross-sectional study involving 300 adult patients who were admitted to undergo surgery in our tertiary care unit from January 2016 to January 2018. Cutoff point was considered at a level of 30 (ng/mL) in defining vitamin D deficiency. The presence of any SSI was investigated and recorded at the time of discharge and at postoperative visits up to 30 d after the surgery. Cross-tabulation and bivariate and multivariate logistic regression with unadjusted and adjusted odd ratio were used to determine the association between dependent and independent variables and to identify factors associated with SSIs. RESULTS: Overall, of 300 patients who were investigated, 39% had preoperative vitamin D deficiency and 11% developed SSI. In univariate logistic regressions, 20 predictors were selected to be included in the multivariate analysis. Finally preoperative level of 25-hydroxy vitamin D, history of recent infection, preoperative and postoperative hospital length of stay, and postoperative blood transfusions were confirmed as statistically significant independent predictors of SSI. CONCLUSIONS: Preoperative 25-hydroxy vitamin D level has a strong effect on postoperative SSI. Prospective double-blinded randomized clinical trials are required to confirm such strong relationship and to settle preoperative vitamin D measurement as a standard approach to reduce postoperative complications including SSI. Preoperative patient optimization, limiting hospital length of stay, and blood transfusion are other strategies to reduce SSI.

Promoter Methylation of Four Tumor Suppressor Genes in Human Papillary Thyroid Carcinoma.

BACKGROUND & OBJECTIVE: Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. Methylation is the most common type of epigenetic alterations that can be an excellent indicator of PTC invasive behavior. METHODS: In this research, we determined the promoter methylation status of four tumor suppressor genes (SLC5A8, RASSF1, MGMT, and DNMT1) and compared the results of 55 PTC cases with 40 goiter patients. For methylation, we used the methylation-sensitive high resolution melting (MS-HRM) assay technique. The resulting graphs of each run were compared with those of 0%, 50%, and 100% methylated controls. RESULTS: Our data showed that the promoter methylation of SLC5A8, Ras association domain family member 1(RASSF1), and MGMT were significantly different between PTC tissue and goiter with P-value less than 0.05. The most significant differences were observed in RASSF1; 77.2% of hyper-methylated PTC patients versus 15.6% hyper-methylated goiter samples (P<0.001). CONCLUSION: RASSF1 promoter methylation can be a PTC genetic marker. RASSF1 promoter methylation is under the impact of the methyltransferase genes (DNMT1 and MGMT), protein expression, and promoter methylation.

Validation of Reference Genes for Normalization of Relative qRT-PCR Studies in Papillary Thyroid Carcinoma.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) in thyroid tumors require accurate data normalization, however, there are no sufficient studies addressing the suitable reference genes for gene expression analysis in malignant and normal thyroid tissue specimens. The purpose of this study was to identify valid internal control genes for normalization of relative qRT-PCR studies in human papillary thyroid carcinoma tissue samples. The expression characteristics of 12 candidate reference genes (GAPDH, ACTB, HPRT1, TBP, B2M, PPIA, 18SrRNA, HMBS, GUSB, PGK1, RPLP0, and PGM1) were assessed by qRT-PCR in 45 thyroid tissue samples (15 papillary thyroid carcinoma, 15 paired normal tissues and 15 multinodular goiters). These twelve candidate reference genes were selected by a systematic literature search. GeNorm, NormFinder, and BestKeeper statistical algorithms were applied to determine the most stable reference genes. The three algorithms were in agreement in identifying GUSB and HPRT1 as the most stably expressed genes in all thyroid tumors investigated. According to the NormFinder software, the pair of genes including 'GUSB and HPRT1' or 'GUSB and HMBS' or 'GUSB and PGM1' were the best combinations for selection of pair reference genes. The optimal number of genes required for reliable normalization of qPCR data in thyroid tissues would be three according to calculations made by GeNorm algorithm. These results suggest that GUSB and HPRT1 are promising reference genes for normalization of relative qRT-PCR studies in papillary thyroid carcinoma.

Hsa-miR-942 fingerprint in colorectal cancer through Wnt signaling pathway.

The Wnt signaling pathway has been identified for its function in carcinogenesis and embryonic development. It is known to play a vital role in the initiation and development of colorectal cancer (CRC). Therefore, it is of great importance for CRC research to illuminate the mechanisms which regulate Wnt pathway activity. Here, we intended to examine the effect of hsa-miR-942 (miR-942) on the Wnt signaling activity, cell cycle progression, and its expression in CRC tissues. RT-qPCR results indicated that miR-942 is significantly upregulated in colorectal cancer. Then, overexpression of miR-942 promoted, whereas its inhibition decreased the Wnt signaling activity, detected by RT-qPCR and Top/Fop flash assay. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules indicated that miR-942 applies its effect to the ß-catenin degradation complex level. Then, RT-qPCR and dual luciferase assay showed that miR-942 upregulated Wnt signaling through direct targeting of APC, which is a tumor suppressor in Wnt signaling pathway. Furthermore, the western blotting analysis indicated that ß.catenin, as a main member of Wnt signaling pathway is upregulated following the overexpression of miR-942. Finally, miR-942 overexpression resulted in cell cycle progression in SW480 cells. Taken together, our findings established an oncogenic role for miR-942 in CRC and indicated that this miRNA might be a crucial target for CRC therapy.

Circulating ctDNA methylation quantification of two DNA methyl transferases in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) is the most common type of cancer among thyroid malignancies. Tumor-related methylation of circulating tumor DNA (ctDNA) in plasma could represent tumor specific alterations can be considered as good biomarkers in circulating tumor cells. In this study, we studied the methylation status of seven promoter regions of two DNA methyl Transferases (MGMT and DNMT1) genes as the methylated ctDNA in plasma and tissue samples of patients with PTC and goiter patients as noncancerous controls. METHODS: Both ctDNA and tissue genomic DNA of 57 PTC and 45 Goiter samples were isolated. After bisulfite modification, the methylation status was studied by Methylation-Sensitive High Resolution Melting (MS-HRM) assay technique. Four promoter regions of O6-methylguanine-DNA methyltransferase (MGMT) and three promoter regions of DNA methyltransferase 1 (DNMT1) were assessed. RESULTS: From seven candidate promoter regions of two methyltrasferase coding genes, the methylation status of ctDNA within MGMT (a), MGMT (c), MGMT (d), and DNMT1 (b) were meaningfully different between PTC cases and controls. However, the most significant differences were seen in circulating ctDNA MGMT (c) which was hypermethylated in 25 (43.9 %) of patients with PTC vs 2 (4. 4 %) of goiter samples. Between two selected DNA methyl transferase, the methylation of MGMT as the maintenance methyltransferase was significantly higher in PTC cases than goiter controls (P-value < .001). The resulting areas under the receiver operating characteristic (ROC) curve were 0.78 for MGMT (d) for PTC versus goiter samples that can represent the overall ability of MGMT (d) methylation status to discriminate between PTC and goiter patients. CONCLUSION: Among seven candidate regions of ctDNA the MGMT (c) and MGMT (d) showed higher sensitivity and specificity for PTC as a suitable candidates as biomarkers of PTC.

Liquid Biopsy as a Minimally Invasive Source of Thyroid Cancer Genetic and Epigenetic Alterations.

In the blood of cancer patients, some nucleic acid fragments and tumor cells can be found that make it possible to trace tumor changes through a simple blood test called "liquid biopsy". The main components of liquid biopsy are fragments of DNA and RNA shed by tumors into the bloodstream and circulate freely (ctDNAs and ctRNAs). Tumor cells which are shed into the blood (circulating tumor cells or CTCs), and exosomes that have been investigated for non-invasive detection and monitoring several tumors including thyroid cancer. Genetic and epigenetic alterations of a thyroid tumor can be a driver for tumor genesis or essential for tumor progression and invasion. Liquid biopsy can be real-time representative of such genetic and epigenetic alterations to trace tumors. In thyroid tumors, the circulating BRAF mutation is now taken into account for both thyroid cancer diagnosis and determination of the most effective treatment strategy. Several recent studies have indicated the ctDNA methylation pattern of some iodine transporters and DNA methyltransferase as a diagnostic and prognostic biomarker in thyroid cancer as well. There has been a big hope that the recent advances of genome sequencing together with liquid biopsy can be a game changer in oncology.

Clinical outcome of thymectomy in myasthenia gravis patients: A report from Iran.

Background: Myasthenia gravis (MG) is an autoimmune disease affecting acetylcholine postsynaptic receptor of voluntary muscles. Thymectomy is done in these patients and is a mainstay in the treatment of MG; however, the long-term result of surgery is still controversial. This study dealt with the investigation of the results of thymectomy in treatment, recovery and control of the symptoms of these patients. Methods: This study was performed through a retrospective method in patients suffering from MG who underwent trans-sternal thymectomy between 2011 and 2016. We conducted thymectomy, excision of mediastinal mass and contents of tissues between the right and left phrenic nerves for all patients. Then, the effect of various variables including age, sex, time interval between onset of disease and surgery, thymus pathology and the dosage of drug on clinical response after surgery was determined using various statistical tests. Results: 47 patients including 26 men and 21 women with the mean age of 33.0 ± 4.6 years have been investigated. The mean age of patients was 36.2 and 29.7 in men and women respectively (P = 0.041). Spiral chest computed tomography (CT) scan was present in 47 patients demonstrating mediastinal mass in 40 (85.1%) patients. Also, our pathological results showed thymic cells in aortopulmonary window contents of 4 patients. According to the results, the younger age of patients at the time of surgery, shorter time between diagnosis and thymectomy, being a woman and non-thymoma pathology were along with better clinical outcomes after thymectomy. Conclusion: Our study shows better clinical results of thymectomy in patients with normal chest CT scan and normal or atrophic thymus in pathologic reports. Generally, it seems that performing thymectomy in a shorter time interval after diagnosis of MG is beneficial. Moreover, in MG patients who do not suffer from thymoma, it is along with positive results.

Introduction of hsa-miR-103a and hsa-miR-1827 and hsa-miR-137 as new regulators of Wnt signaling pathway and their relation to colorectal carcinoma.

Wnt signaling is hyper-activated in most of human cancers including colorectal carcinoma (CRC). Therefore, the introduction of new regulators for Wnt pathway possesses promising diagnostic and therapeutic applications in cancer medicine. Bioinformatics analysis introduced hsa-miR-103a, hsa-miR-1827, and hsa-miR-137 as potential regulators of Wnt signaling pathway. Here, we intended to examine the effect of these human miRNAs on Wnt signaling pathway components, on the cell cycle progression in CRC originated cell lines and their expression in CRC tissues. RT-qPCR results indicated upregulation of hsa-miR-103a, hsa-miR-1827, and downregulation of hsa-miR-137 in CRC tissues. Overexpression of hsa-miR-103a and hsa-miR-1827 in SW480 cells resulted in elevated Wnt activity, detected by both Top/Flash assay and RT-qPCR analysis. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules suggested that these miRNAs exerts their effect at the ß-catenin degradation complex level. Then, RT-qPCR, dual luciferase assay, and western blotting analysis indicated that APC and APC2 transcripts were targeted by hsa-miR-103a, hsa-miR-1827 while, Wnt3a and ß-catenin genes were upregulated. However, hsa-miR-137 downregulated Wnt3a and ß-catenin genes. Further, hsa-miR-103a and hsa-miR-1827 overexpression resulted in cell cycle progression and reduced apoptotic rate in SW480 cells, unlike hsa-miR-137 overexpression which resulted in cell cycle suppression, detected by flowcytometry and Anexin analysis. Overall, our data introduced hsa-miR-103a, hsa-miR-1827 as onco-miRNAs and hsa-miR-137 as tumor suppressor which exert their effect through regulation of Wnt signaling pathway in CRC and introduced them as potential target for therapy.

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARß2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARß2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

The Effect of Omentoplasty on the Rate of Anastomotic Leakage after Intestinal Resection: A Randomized Controlled Trial.

Anastomotic leakage is a major postoperative complication after intestinal surgery leading to increased risk of morbidity and mortality. Omentoplasty has been evaluated to prevent anastomotic leakage in several studies. However, there is no consensus regarding whether or not omentoplasty should be used to decrease the rate of anastomotic leakage after intestinal resection. A prospective, randomized study was conducted to evaluate the influence of omentoplasty on anastomotic leakage after intestinal resection. A total of 124 patients who underwent intestinal resection were enrolled in this prospective study. Patients were randomly assigned to receive either the omentoplasty or nonomentoplasty. In the omentoplasty group, the omentum was wrapped around the anastomotic region. Age, gender, site and type of anastomosis, duration of hospital stay, and performance of omentoplasty were recorded. This study was registered in Iranian Registry of clinical trial (number: IRCT201412316925N3). The rate of anastomotic leakage was significantly lower in the omentoplasty group (P = 0.04). Patients in the omentoplasty group developed a significantly lower rate of postoperative infection and peritonitis (P < 0.05). There was no significant difference of abscess and fistula formation between the two groups (P > 0.05). The length of hospital stay was longer in the nonomentoplasty group, compared with that for omentoplasty patients (P < 0.05). No death occurred in the omentoplasty subjects, while six nonomentoplasty patients died (P < 0.05). Our data demonstrated that omentoplasty is useful to lower the rate of postoperative complications in patients underwent intestinal surgery.

Evaluation of platelet-rich plasma gel potential in acceleration of wound healing duration in patients underwent pilonidal sinus surgery: A randomized controlled parallel clinical trial.

OBJECTIVES: One of the most important surgical issues applied in the treatment of pilonidal sinus disease is wound healing. The aim of this study was to investigate the possible effect of platelet-rich plasma (PRP) gel on accelerating wound healing in these patients. METHODS: In this randomized, controlled, parallel group clinical trial, 110 patients were randomly allocated into two parallel groups with the same size (controls and treatment arm) after meeting inclusion and exclusion criteria. After the surgery, controls were treated by classic wound dressing while the case group was treated with PRP gel in a classic wound dressing platform. The patients were then evaluated for duration of antibiotics consumption, experienced pain and the time of returning to routine activities. Also, both groups were assessed for angiogenesis (by detecting CD34+ cells using immunohistochemical assay) and collagen sedimentation (masson's trichrome staining) using pre-complete healing wound biopsy. All the statistical analyses were performed using SPPS 20 and p-values of less than 0.05 considered statically significant. RESULTS: According to the results, patients treated with PRP gel went through a significantly faster healing process (8.69±1.18 in controls and 4.78±0.87 weeks in PRP gel treated ones with the P-value=0.03) and returned to their routine activities (3.3±0.64 for the treatment of arm and 6.5±1.03 weeks for controls with the P-value=0.00) while experiencing less pain (P-value=0.00) and shorter anti-biotic consumption duration (P-value=0.00). CONCLUSION: Considering the results, authors of this study suggest PRP gel treatment for post operation wound dressing of pilonidal sinus disease with healing by secondary intention.

Alternative splicing of the OCC-1 gene generates three splice variants and a novel exonic microRNA, which regulate the Wnt signaling pathway.

The Wnt signaling pathway is hyperactivated in most colorectal cancers (CRC). Finding new regulators of this pathway represents the potential for cancer diagnosis or treatment. OCC-1 was initially reported as an up-regulated gene in colon carcinoma, without knowing its mechanism of action. Here, two novel transcript variants and an exonic microRNA that originated from the OCC-1 gene are reported, showing positive effects on Wnt activity. Up-regulation of the known OCC-1 variant (assigned as OCC-1A/B) was limited to CRC, and its overexpression increased survival of CRC-originated SW480 cells (Wnt+), while resulting in apoptosis of Wnt-suppressed SW480 cells or HeLa cells (Wnt-) detected by PI staining. Immunocytochemistry showed that the OCC-1A/B-encoded peptide was localized to the nucleus, where its overexpression resulted in Wnt signaling up-regulation, detected by TOP/FOPflash assay. The noncoding portion of the OCC-1A/B transcript had a suppressive effect on Wnt activity and had a negative correlation with APPL2 neighboring gene expression. Unlike OCC-1A/B, the novel OCC-1C splice variant had no expression alteration in CRC, and it seemed to encode a smaller peptide with cytoplasmic localization. A 60-nucleotide (nt) fragment containing an AUG start codon is spliced out to produce an OCC-1D noncoding RNA variant. The 60-nt RNA was validated as the precursor of a novel microRNA, which we named miR-ex1 Both OCC-1D and miR-ex1 were coordinately up-regulated in CRC. MiR-ex1 functional analysis revealed that it is targeting the APC2 tumor suppressor gene and is an activator of the Wnt signaling pathway. Overall, the OCC-1 gene is now introduced as a novel Wnt signaling regulator and as a potential therapeutic target.