Identification and prevention of genotyping errors caused by G-quadruplex- and i-motif-like sequences.

Abstract Background: Reliable PCR amplification of DNA fragments is the prerequisite for most genetic assays. We investigated the impact of G-quadruplex– or i-motif–like sequences on the reliability of PCR-based genetic analyses. Methods: We found the sequence context of a common intronic polymorphism in the MEN1 gene (multiple endocrine neoplasia I) to be the cause of systematic genotyping errors by inducing preferential amplification of one allelic variant [allele dropout (ADO)]. Bioinformatic analyses and pyrosequencing-based allele quantification enabled the identification of the underlying DNA structures. Results: We showed that G-quadruplex– or i-motif–like sequences can reproducibly …

Intrathyroidal Thymic Tissue Surrounding an Intrathyroidal Parathyroid Gland, the Cause of a Solitary Thyroid Nodule in a 6-Year-Old Boy

Ectopic intrathyroidal thymic tissue is a rare occurrence; parathyroid glands sometimes occur in an intrathyroidal location, but this is uncommon. We report a 6-year-old boy who was noted to have a solitary thyroid nodule on ultrasound. A hemithyroidectomy was performed, and histological investigation revealed that the nodule consisted of ectopic intrathyroidal thymus tissue surrounding a well-defined parathyroidal gland. This condition is an exceedingly rare cause of a thyroid nodule, but intrathyroidal thymic tissue should probably be included in the differential diagnosis of solitary thyroid nodules.

Thyroid surgery and radioiodine ablation—the surgeon's role

Total thyroidectomy and subsequent radioiodine ablation improve the outcome of patients with thyroid tumours measuring >1 cm. Best practice guidelines should serve as a basis for clinical decision making in stage I thyroid cancer; however, Haymart et al. report that soft factors, unrelated to clinical presentation, affect the rate of radioiodine ablation.

Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques - A molecular and clinical analysis.

Abstract Introduction Oncogenic BRAF and RAS mutations as well as multiple known (and yet unknown) RET fusion oncogenes comprise the majority of causative molecular alterations in papillary thyroid carcinoma (PTC). Apparently “mutation-negative” PTCs encompass a heterogenous group impeding analysis of prognostic significance of underlying genetics. Material and methods BRAF wild type PTC tissue of 56 patients was analyzed using two established methods: hybrid-specific RT-PCR for the predominant rearrangement RET/PTC1 and fluorescent in situ hybridization (FISH). Clinical features of the cases with and without RET rearrangement were compared (patient age, gender, tumor size, focality, lymph …

PS02.147: MANAGEMENT OF A SIMULTANEOUS HIGH ESOPHAGO-TRACHEAL FISTULA CAUSED BY ESOPHAGEAL STENT DUE TO ANASTOMOTIC LEAKAGE AFTER IVOR-LEWIS ESOPHAGECTOMY: A CASE REPORT

Abstract Background Esophagotracheal perforation is a very severe complication. However, an esophagotracheal perforation caused due to an esophageal stent after anastomotic leakage after ivor-lewis resection, is even more complex and associated with high mortality. Therefore we present a case how we managed a high esophagotracheal perforation and anastomotic leakage after ivor-lewis resection of esophageal cancer, prior treated with neoadjuvant radiochemotherapy. Methods Case report A 71-year old patient was transferred to our center due to an esophagotracheal perforation at the proximal stent—and at 18–20 cm from the front teeth row. The stent had been placed due to anastomotic leakage aft…

P126 HIGH ESOPHAGOTRACHEAL FISTULA DURING STENT TREATMENT OF AN ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY

Abstract Aim We present a case of a 71 year old female with a combined anastomotic leakage after ivor-lewis resection and esophagotracheal perforation. Background & Methods Anastomotic leakage after esophageal resection is still associated with high morbidity and mortality throughout hospitalization. Nowadays there are several methods to accomplish sufficient closure of the anastomotic leakage such as clipping and using fibrin sealant in smaller leakages. Severe insufficiencies are commonly treated using esophageal stents. In our case the use of such a stent (10cm covered) placed to an anastomotic leak following esophagectomy with high intrathoracic anastomosis lead to an esophagotrache…

Synchronous Antithyroid Drug-Induced Agranulocytosis and Fournier Gangrene

ABSTRACT: Objective: Antithyroid drugs (ATDs) such as thioimidazoles (e.g., methimazole, also called thiamazole, and carbimazole) and propylthiouracil are commonly used for the treatment of hyperthyroidism. A life-threatening reaction is agranulocytosis with an incidence of 0.1 to 0.5%. There are very few cases in the literature showing that the intake of ATDs finally led to sepsis with accompanying tissue necrosis.Methods: We present an unusual case of severe symptomatic agranulocytosis with sudden development of Fournier gangrene in a patient who was treated with ATDs for hyperthyroidism due to Graves disease.Results: A 69-year-old female was referred to our hospital with fever and a sore…

European perspective on the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Proceedings of an interactive international symposium

The American Thyroid Association (ATA) management guidelines for patients with thyroid nodules and differentiated thyroid cancer (DTC) are highly influential practice recommendations. The latest revision appeared in 2015 ("ATA 2015"). These guidelines were developed predominantly by North American experts. European experts frequently have different perspectives, given epidemiological, technological/methodological, practice organization, and medicolegal differences between the respective regions.Divergent viewpoints were the focus of an invited symposium organized by the European Association of Nuclear Medicine involving 17 European thyroidologists, four ATA Guidelines Taskforce members, and…

Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants

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Differential miRNA expression defines migration and reduced apoptosis in follicular thyroid carcinomas.

The objective of the study was to identify microRNAs (miRs) characteristic for follicular thyroid carcinoma (FTC) and to define their role in tumorigenesis. A miR-microarray study was conducted to identify miRs differentially expressed between FTCs and their surrounding tissues. Selection was further reinforced by a literature review. Four miRs were selected and confirmed by RT-qPCR: miR-146b, -183, -221 were up-regulated, whereas miR-199b down-regulated in FTCs. The influence of these miRs on cell proliferation, cell cycle, apoptosis and migration was studied in HTori and FTC-133 cells. Functional characterization suggests an impact of miR-183 and miR-146b in FTC development. Overexpressio…

Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity

Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreatic NETs were reviewed for evidence of a somatostatinoma syndrome. Predominant or exclusive expression of somatostatin was found in 21 (26%) duodenal and 21 (4%) pancreatic NETs. They were classified as sporadic (n=31) or neurofibromatosis type 1 (NF1)-associated duodenal NETs (n=3), gangliocytic paragangliomas (GCPGs; n=6), or poorly differentiated neuroendocrine carcinomas (pd…

Adrenalectomy for solid tumor metastases: Results of a multicenter European study

Background. We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers. Methods. Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible. Results. Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (#6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86%…

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma

Abstract Background Rearrangements of RET are drivers of oncogenesis, traceable in different cancer types as papillary thyroid carcinoma (PTC), non-small cell lung cancer, colorectal or breast cancer. Anchored multiplex PCR based next-generation sequencing (NGS) can detect RET rearrangements involving previously unknown partner genes. Methods A sample of PTC underwent NGS, following detection of RET rearrangement by fluorescence in situ hybridization. Expression analysis of ANKRD26 and RET was performed for the tumor harboring ANKRD26-RET, for corresponding normal thyroid tissue and PTC tumors with representative genetic alterations (BRAFV600E, CCDC6-RET), complemented by a comparative sear…

Educational Team Time Out in der onkologischen Viszeralchirurgie: Ein Konzept zur Optimierung der Weiterbildung

Identification of Differentially Expressed Genes in Papillary Thyroid Carcinomas With and Without Rearrangements of the Tyrosine Kinase Receptors RET and/or NTRK1

Background The transforming capacities of RET and/or NTRK1 chimeric oncogenes as well as the molecular background of non-rearranged papillary thyroid carcinomas (PTCs) remain to be elucidated. To assess altered gene expression, we examined PTCs with and without tyrosine kinase receptor rearrangements by mRNA differential display (DD). Materials and methods Six of 13 PTCs examined harbored RET chimeras (3× RET/PTC1, 1× RET/PTC3) and/or NTRK1 chimeras (2× trk, 1× TRK-T3, 2 unknown TRK hybrids). The method of DD analysis was refined by a novel fragment-recovery technique using a high-performance fluorescence scanner. Results Of 500 up- or down-regulated mRNA transcripts, 19 selected fragments …

Novel rearrangements involving the RET gene in papillary thyroid carcinoma.

Abstract Background In the field of gene fusions driving tumorigenesis in papillary thyroid carcinoma (PTC), rearrangement of the proto-oncogene RET is the most frequent alteration. Apart from the most common rearrangement of RET to CCDC6, more than 15 partner genes are yet reported. The landscape of RET rearrangements in PTC (“RET-PTC”) can notably be enlarged by modern targeted next-generation sequencing, indicating similarities between oncogenic pathways in other cancer types with identical genetic alterations. Methods Targeted next-generation sequencing was performed for two cases of BRAF-wild type PTC with confirmation of the results by Sanger sequencing. A “UniProt” database research …

Fine Needle Aspiration in the Investigation of Thyroid Nodules

Background Thyroid nodules are a common finding in Germany. Most are benign; thyroid cancer is very rare. The challenge for the physician is to diagnose malignant tumors early. Fine needle aspiration is an important tool for this purpose.

A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas.

The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the "indeterminate" category, can be partially overcome by molecular analyses. We aimed at the identification of miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were validated by qPCR in an independent set of 32 FTCs and 46 FAs. Sixty-eight differentially expressed miRNAs were identified. Thirteen miRNAs could be confirmed by cross comparison. A two-miR…

Real-world EUROCRINE® registry data challenge the reliability of Bethesda cytopathology for thyroid surgery indication

Abstract Objectives Fine-needle aspiration cytology (FNAC) is recommended by international guidelines for the preoperative evaluation of suspicious thyroid nodules >1 cm. Despite robust evidence from endocrine centers demonstrating the key role of FNAC results for the indication of surgery, the method is not routinely used in European clinics. The database EUROCRINE®, which was introduced in 2015 with the scope of registering operations of the endocrine system, allows for a large-scale analysis of the current service reality in Europe concerning FNAC use and associated accuracy. Methods Operations performed to “exclude malignancy”, registered from January 2015 to December 2018 in EUROCRI…

6-18F-Fluoro-l-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to123I-Metaiodobenzyl-Guanidine Scintigraphy in the Detection of Extraadrenal and Hereditary Pheochromocytomas and Paragangliomas: Correlation with Vesicular Monoamine Transporter Expression

Context: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by 18F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than 123I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. Objective: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. Design and Setting: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. Patients: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate de…

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%…

Total Versus Near-total Thyroidectomy in Graves Disease

Previous data suggest that the incidence of hypoparathyroidism after surgery for Graves disease (GD) is lower after subtotal thyroidectomy compared to total thyroidectomy (TT). The present study evaluated the incidence of postoperative hypoparathyroidism after near-total (NTT) versus TT in GD.In a multicenter prospective randomized controlled clinical trial, patients with GD were randomized intraoperatively to NTT or TT. Primary endpoint was the incidence of transient postoperative hypoparathyroidism. Secondary endpoints were permanent hypoparathyroidism, transient recurrent laryngeal nerve palsy (RLNP), reoperations for bleeding, inadvertently removed parathyroid glands, and recurrent hype…

Laparoscopy versus open adrenalectomy in patients with solid tumor metastases: results of a multicenter European study

Background: The outcome of adrenalectomy carried out by laparoscopy or open surgery for solid tumor metastases was assessed. Methods: A total of 317 patients with histologically confirmed adrenal metastatic disease collected from 30 centres in Europe underwent adrenalectomy by laparoscopy (n=146) or open laparotomy (n=171). Differences between laparoscopic and open adrenalectomy were assessed by a single Cox analysis for both procedures. Results: The median overall survival was 24.0 [95% confidence interval (CI): 21.4-26.6] months for open adrenalectomy and 45.0 (95% CI: 22.6-67.4) for laparoscopic adrenalectomy (P=0.008). Survival rates were 68%, 49%, 35% and 29% at 1, 2, 3 and 5 years for…

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independe…

Comparison between Minimally Invasive Video-Assisted Thyroidectomy and Conventional Thyroidectomy: Is There Any Evidence-Based Information?

The aim of this study was to test the hypothesis that minimally invasive video-assisted thyroidectomy (MIVAT) affords comparable safety and efficacy as to the open conventional surgery in dealing with patients with small thyroid nodules.Randomized controlled trials comparing the MIVAT with open thyroidectomy were ascertained by methodical search using Medline, Embase, Pubmed, and The Cochrane Library. Primary meta-analysis outcomes were adverse events (laryngeal nerve palsy and hypoparathyroidism), and cosmesis and secondary outcomes were operative time, blood loss, and early and late postoperative pain.Operative time was significantly less with open thyroidectomy than with MIVAT, while MIV…

Congenital primary hypothyroidism with subsequent adenomatous goiter in a Turkish patient caused by a homozygous 10-bp deletion in the thyroid peroxidase (TPO) gene

Summary Objective  Congenital primary hypothyroidism occurs in 1 of 4000 births. Whereas the majority of the cases are due to developmental defects of the thyroid gland, 20% carry a defect in thyroid hormonogenesis. We report a Turkish boy who had goitrous hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene. Design  The TPO gene was sequenced directly from genomic DNA and cDNA which was transcribed from three RNA samples harvested from different parts of the patient's excised thyroid gland. Patient  The boy was thyroidectomized because of continuing growth of his thyroid gland and development of multiple nodes suspected of malignancy by ultrasound examination. Histopatholo…

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generat…

Seltene hormonaktive Tumoren des Pankreas – chirurgische Therapie

Hormonaktive neuroendokrine Neoplasien des Pankreas umfassen neben Insulinomen und Gastrinomen sogenannte „seltene hormonaktive Tumoren“, welche sehr unterschiedliche Hormone sezernieren konnen. Die Therapie dieser uberwiegend malignen Tumoren erfolgt entsprechend der durch die European Neuroendocrine Tumor Society (ENETS) und die North American Neuroendocrine Tumor Society (NANETS) formulierten Leitlinien. Die operative Therapie stellt hierbei einen zentralen Bestandteil der Therapiestrategien dar, welche einen kurativen oder palliativen Ansatz verfolgen konnen. Die Indikation zur operativen Therapie und die Wahl des notwendigen Resektionsausmases erfordern detaillierte Kenntnisse zur klin…