Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients. METHODS: We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables. RESULTS: Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase. CONCLUSIONS: The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified

Comparative diagnostic test accuracy of post-esophagectomy water-soluble computed tomography and fluoroscopic swallow studies: A meta-analysis

Aims: Both fluoroscopic water-soluble contrast swallow (FWSCS) and CT water-soluble contrast swallow (CTWSCS) are widely performed as a routine in the post-esophagectomy patient to assess for anastomotic leak. Several prospective studies have compared FWSCS and CTWSCS; however, no synthesis of the data exists. Materials and Methods: Systematic review and meta-analysis of diagnostic test accuracy studies comparing FWSCS and CTWSCS in the adult patient following esophagectomy for malignancy was performed in accordance with PRISMA guidelines. Results: Three diagnostic test accuracy studies met the inclusion criteria, directly comparing FWSCS and CTWSCS in 185 patients. FWSCS demonstrated high specificity (98%), but low sensitivity (64%). CTWSCS can be categorized as normal, mediastinal gas without contrast leak, or leakage of oral contrast. Visible leakage of oral contrast demonstrated high specificity (98%) but low sensitivity (56%). The presence of mediastinal gas increased sensitivity (84%), but reduced specificity (85%). The higher sensitivity of CTWSCS over FWSCS failed to reach significance (P = 0.125). Conclusion: CTWSCS shares the high specificity of FWSCS. Its higher sensitivity increases its utility as a rule-out test in the postoperative period. Additional factors that may influence decision-making are described

A novel monoallelic <i>ALG5 </i>variant causing late-onset ADPKD and tubulointerstitial fibrosis

Introduction Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage. Methods Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies. Results We identified a monoallelic ALG5 variant [GRCh37 (NM_013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients’ kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins. Conclusion ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD-ALG5.</p

CT imaging for occult malignancy in patients with unprovoked venous thromboembolism (VTE) in a tertiary centre: is it worthwhile?

Background: Investigating patients with unprovoked venous thromboembolism (uVTE) for occult malignancy can prove a diagnostic dilemma and imaging is often used extensively in this patient group. Aims: The primary objective of this study was to determine the incidence of malignancy on CT and other imaging over a 10-year period. A secondary objective was to evaluate the role of laboratory and other non-imaging tests performed. Methods: A retrospective key word search of our hospital's imaging system was performed to identify patients with unprovoked DVT/PE over the last 10 years. All imaging, histology, endoscopy, laboratory tests, and clinical follow-up over 2 years were analysed. Patients with provoked VTE were excluded. Results: 150 patients had uVTE. 9 patients were diagnosed with occult malignancy by different investigations on index hospital admission (3 patients) or subsequently on clinical follow-up (6 patients). Mean age of patients was 62 years. 116 patients had CT body imaging. The incidence of malignancy diagnosed by initial CT imaging was 1.7% with a sensitivity of 22%, specificity 87%, and PPV 12.5%. Overall incidence of malignancy identified by imaging alone during the index hospital admission was 2%. Total incidence of malignancy including index admission and follow-up was 6%. Median time to cancer diagnosis was 12 months. Conclusion: CT imaging had a low yield for diagnosing malignancy. Extensive imaging strategies increase cost and radiation exposure without improving mortality. Clinical follow-up, history taking, and physical examination guiding appropriate investigations remain the best tool for unmasking occult malignancy in patients with uVTE.</div