Jakob W. Kist

The value of miRNA in diagnosing thyroid cancer: a systematic review.

Thyroid cancer is the most common endocrine neoplasm accounting for approximately 1,7% of total cancer diagnoses. The gold standard for evaluation of thyroid nodules is cytology from fine needle aspiration. In 30% of biopsies there is no conclusive diagnosis and patients undergo a diagnostic hemithyroidectomy. Somatic mutations occur frequently in thyroid cancer, the value of testing FNA biopsies on different mutation is analyzed, it improves accuracy, but their sensitivity is low. Another class of molecules with potential diagnostic value are miRNAs (miRNA, miR). MiRNAs function as gene regulators thereby controlling many cellular processes including cell growth, differentiation, proliferation, and apoptosis. Several studies have analyzed the expression of miRNAs in thyroid cancer, either by performing microarray analyses or validating a set of miRNAs. Recent reports focused on the diagnostic value of miRNAs in indeterminate FNA biopsies. In this systematic review we will provide an overview of all miRNAs found to be up- or downregulated in the different types of thyroid carcinomas, give an overview of the value of validated sets of microRNAs or single microRNAs in distinguishing malignant from benign lesions and conclude with a clinical view on future study strategies.

Qualitative elastography can replace thyroid nodule fine-needle aspiration in patients with soft thyroid nodules. A systematic review and meta-analysis

CONTEXTnOnly a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules.nnnOBJECTIVEnTo investigate the diagnostic value of qualitative elastography in distinguishing benign from malignant thyroid nodules in patients referred for fine-needle aspiration (FNA).nnnDATA SOURCESnA systematic literature search (PubMed, Embase and Cochrane Library) was performed.nnnSTUDY SELECTIONnIncluded studies reported thyroid nodule elastography color scores and the related cytologic or histologic findings in patients with a thyroid nodule referred for FNA.nnnDATA EXTRACTIONnTwo independent reviewers extracted study data and assessed study quality. Pooled sensitivities and specificities of different populations were calculated using a bivariate Bayesian framework.nnnDATA SYNTHESISnTwenty studies including thyroid nodules were analyzed. Pooled results of elastography indicate a summary sensitivity of 85% (95% confidence interval [CI], 79-90%) and specificity of 80% (95% CI, 73-86%). The respective pooled negative predictive and positive predictive values were 97% (95% CI, 94-98%) and 40% (95% CI, 34-48%). The pretest probability of a benign nodule was 82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma. A pooled negative predictive value of 99% (95% CI, 97-100%) was found when only complete soft nodules (Asteria elastography 1) were classified as benign, which included 14% of the studied population.nnnCONCLUSIONSnElastography has a fair specificity and sensitivity for diagnostic accuracy. Its major strength entails the detection of benignity, especially when only completely soft nodules are qualified as benign. The outcomes of our analysis show that FNA could safely be omitted in patients referred for analysis of their thyroid nodule when elastography shows it to be completely soft (Asteria elastography 1). This could prevent unnecessary invasive diagnostic procedures in a substantial portion of patients.

Thyroid Ultrasound-Guided Fine-Needle Aspiration: The Positive Influence of On-Site Adequacy Assessment and Number of Needle Passes on Diagnostic Cytology Rate.

Objective: Nondiagnostic cytology is the most important limitation of thyroid ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to identify factors associated with the adequacy rate of thyroid US-FNA. Study Design: Consecutive thyroid US-FNAs (2006-2013) were retrospectively included. Attending radiologists, radiology fellows and radiology residents performed US-FNA, usually involving 2-3 needle passes. In more recent years, rapid on-site adequacy assessment (ROSAA) was performed to ensure specimen adequacy. US characteristics, procedural variations and cytology results were extracted from US and pathology reports and statistically evaluated. Results: Diagnostic cytology was obtained in 64.6% of 1,381 thyroid US-FNAs. Factors associated with nondiagnostic cytology were ROSAA (74.6% diagnostic cytology, OR 0.55, 95% CI 0.42-0.71), ≥3 clinic visits for US-FNA of the same thyroid nodule (54.7%, OR 1.56, 95% CI 1.16-2.10) and increased intranodular vascularization (51.8%, OR 1.73, 95% CI 1.17-2.57). With ROSAA, an increasing number of needle passes demonstrated improving adequacy rates. The adequacy rate was not operator-dependent. Conclusion: This study demonstrates that ROSAA improves the adequacy rate of thyroid US-FNA. Without ROSAA, we recommend performing at least 3 needle passes. Less diagnostic cytology is obtained from nodules with increased intranodular vascularization or from those undergoing US-FNA ≥3 times.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm

PurposeTraditionally, total thyroidectomy has been advocated for patients with tumors larger than 1xa0cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4xa0cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1xa0cm.MethodsA retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma.ResultsA total of 1313 patients were included, of whom 426 (32xa0%) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67xa0%) papillary thyroid carcinomas (PTC), 124 (30xa0%) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1xa0%) follicular thyroid carcinomas (FTC), and 3 (1xa0%) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82xa0% were ≤10xa0mm and of those 99xa0% were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92xa0% of cases.ConclusionsThis international multicenter study performed on patients with DTC larger than 1xa0cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

Laparoscopic anterior versus endoscopic posterior approach for adrenalectomy: a shift to a new golden standard?

PurposeThere has been an increased utilization of the posterior retroperitoneal approach (PRA) for adrenalectomy alongside the “classic” laparoscopic transabdominal technique (LTA). The aim of this study was to compare both procedures based on outcome variables at various ranges of tumor size.MethodsA retrospective analysis was performed on 204 laparoscopic transabdominal (UMC Groningen) and 57 retroperitoneal (UMC Utrecht) adrenalectomies between 1998 and 2013. We applied a univariate and multivariate regression analysis. Mann-Whitney and chi-squared tests were used to compare outcome variables between both approaches.ResultsBoth mean operation time and median blood loss were significantly lower in the PRA group with 102.1 (SD 33.5) vs. 173.3 (SD 59.1) minutes (pxa0<xa00.001) and 0 (0–200) vs. 50 (0–1000) milliliters (pxa0<xa00.001), respectively. The shorter operation time in PRA was independent of tumor size. Complication rates were higher in the LTA (19.1%) compared to PRA (8.8%). There was no significant difference in recovery time between both approaches.ConclusionsApplication of the PRA decreases operation time, blood loss, and complication rates compared to LTA. This might encourage institutions that use the LTA to start using PRA in patients with adrenal tumors, independent of tumor size.

The role of qualitative elastography in thyroid nodule evaluation: exploring its target populations

Thyroid nodules are frequently found and pose a dilemma to the clinician, as only a few harbor a malignancy, and the majority of nodules are benign. The standard work-up of thyroid nodules consists of ultrasound and fine needle aspiration (FNA), both having their limitations [1, 2]. In particular, ultrasound lacks criteria for determining whether a nodule is malignant [3]. FNA shows good sensitivities and specificities, but inconclusive and indeterminate results are frequently found, resulting in the need for a diagnostic thyroid lobectomy to obtain a final diagnosis [4]. In the long lasting search to reduce the number of invasive diagnostic procedures, real-time qualitative elastography has been proposed to fulfill this need. Elastography determines the elasticity of the thyroid nodule. Soft nodules are assumed to be benign, whereas hard nodules are considered to be malignant. Qualitative elastography represents the elasticity of the nodule in a colored image projected over the ultrasound image. Multiple elasticity scoring systems are used, which makes reviewing literature challenging. Most common is the 4-point scale developed by Asteria et al., in which elastography 1 (ES 1) is assigned to nodules with elasticity in the entire nodule, ES 2 is assigned to nodules with elasticity in a large portion of the nodule, ES 3 is assigned to nodules with stiffness in a large portion of the nodule, and ES 4 is assigned to hard nodules. A cut-off between ES 2 and ES 3 is widely accepted to discriminate benign from malignant nodules [5]. Studies on thyroid nodule elastography have focused on different target populations: (1) patients referred for FNA with the aim to reduce the number of FNAs, and (2) patients with an indeterminate FNA result (i.e., Bethesda classification III or IV), with the aim to reduce the number of futile lobectomies. Recently, we performed a meta-analysis of studies that investigated the first population: patients referred for FNA. The aim of this study was to determine whether elastography could determine the nature of thyroid nodules and thereby identify those that require further analysis by FNA [6]. In this study, analyzing twenty reports including 3908 nodules, two different cut-offs were examined. The first was the standard cut-off between ES 2 and 3. The second used a cut-off between ES 1 and 2, meaning that only the completely soft nodules were considered benign and the rest of the nodules as potentially malignant. Both cut-offs showed that elastography is an excellent tool to diagnose benignity, with a respective negative predictive value (NPV) of 97 and 99 %. Based on these outcomes, it was concluded that in these cases FNA could be omitted safely. However, considering the modest positive predictive value (PPV) of only 40 % of elastography, this implies that any nodule with an elastography score above ES 2 requires further analysis [6]. In the current issue of Endocrine, Trimboli et al. published an extensive review and meta-analysis on nodules with an indeterminate FNA [7]. Although the majority of these nodules are benign, around one in four harbors a malignancy [4]. Diagnostic lobectomies are often Jakob W. Kist and Sjoerd Nell have contributed equally to the manuscript.

Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer

ABSTRACT Purpose: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5–20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. Methods: We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. Results: Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. Conclusions: Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence.