Fine Needle Aspiration Cytology of the Pancreas: A Guide to the Diagnostic Approach

Fine needle aspiration (FNA) cytology, together with imaging, has become a primary diagnostic modality for investigation of pancreatic mass lesions, both cystic and solid. Advances in imaging techniques have enhanced our ability to recognize and delineate pancreatic masses and to detect them earlier as smaller mass lesions. However, definitive management often cannot be based on clinical and radiological features alone. Despite the advances in the imaging techniques, management options for patients are limited and a malignant diagnosis of solid lesions still carries a high mortality rate. The importance of a cytopathologist in preoperative diagnosis, as a member of the multidisciplinary team, is exemplified in the management of patients with neoplastic cysts. This is based on the pre-operative distinction of non-mucinous and mucinous cysts in general, and benign and malignant cysts in particular. A cytological diagnosis can be obtained with minimally invasive techniques that utilize CT, US or EUS. Endoscopic Ultrasound guided FNA (EUS FNA) is evolving as the diagnostic method of choice due to its ability to more accurately stage the patient during a single procedure using EUS

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening

Diagnostic Cytopathology

xv. 930 hln.; ill.; 27.5 c

The Interobserver Reproducibility of Thyroid Fine-Needle Aspiration Using the UK Royal College of Pathologists' Classification System

The overall interobserver reproducibility of thyroid fine-needle aspiration (FNA) has not been comprehensively assessed. A blinded 6-rater interobserver reproducibility study was conducted of 200 thyroid FNA cases using the UK System, which is similar to The Bethesda System for Reporting Thyroid Cytology: Thy 1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypia, probably benign; Thy3f follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. There was good interobserver agreement for the Thy] (kappa = 0.69) and Thy5 (kappa = 0.61), moderate agreement for Thy2 (kappa = 0.55) and Thy3f (kappa = 0.51), and poor agreement for Thy3a (kappa = 0.11) and Thy4 (kappa = 0.17) categories. Combining categories implying surgical management (Thy3f Thy4, and Thy5) achieved good agreement (kappa = 0.72), as did combining categories implying medical management (Thy 1, Thy2, and Thy3a; kappa = 0.72). The UK thyroid FNA terminology is a reproducible and clinically relevant system for thyroid FNA reporting. This study demonstrates that international efforts to harmonize and refine thyroid cytology classification systems can improve consistency in the clinical management of thyroid nodules

Strokovna stališča Slovenskega združenja za reproduktivno medicino (SZRM) o menopavzni medicini

Obravnava žensk v obdobju predmenopavze, ob menopavzi in kasneje se je v novem tisočletju pomembno spremenila. Randomizirane klinične raziskave so bistveno omejile indikacije za uvedbo hormonskega zdravljenja (HZ) in s tem menopavzno medicino postavile pred velik izziv. Na srečo so najnovejša dognanja potrdila, da je ob pravilni uporabi in izbiri HZ korist še vedno bistveno večja od tveganja. Zato smo pripravili posodobljena stališča o menopavzni medicini, ki so v skladu z aktualnimi mednarodnimi priporočili in prilagojena posebnostim slovenskega prostora

Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer

Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of ∼14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8–7.4], P < 10−10), independently of sex, tissue type, disease state, and methylation platform. We identified a specific subset of 69 PCGT CpGs that undergo hypermethylation with age and validated this methylation signature in seven independent data sets encompassing over 900 samples, including normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells (P < 10−5). We find that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis. These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features