Training undergraduate students for rapid on-site evaluation of fine needle aspiration cytology samples using a simulation-based education activity.

INTRODUCTION: Demand for rapid on-site evaluation (ROSE) of fine needle aspiration (FNA) cytology is rising and the role is increasingly being performed by non-medical cytologists. Undergraduate training for cytologists has traditionally focused on laboratory-based procedural activities and their theoretical underpinning, with minimal attention given to communication and other skills required to operate in an interprofessional setting. We evaluated the effectiveness and student reaction to a simulation-based education (SBE) exercise in ROSE designed to fill this void. METHODS: We designed and evaluated an SBE exercise based on FNA ROSE across two tertiary institutions with 79 students. The exercise accurately reproduced the demands on cytologists operating as part of a multi-disciplinary team in a time- pressured environment. FINDINGS: Pre- and post-simulation questionnaires indicated an improvement in technical knowledge related to the procedure. Students' perception of their competence and confidence in their role also improved significantly post simulation. Students uniformly found the exercise engaging and a valuable addition to their curriculum. DISCUSSION: The simulation successfully provided a pseudo-clinical environment that highlighted the realities of practising technical and diagnostic tasks under time pressure and interacting with other health professionals to provide an optimal patient outcome. The exercise is a useful supplement to on-the-job training for ROSE.

Neutrophil-to-lymphocyte ratio in malignant pleural fluid: Prognostic significance.

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04-1.18] vs 4.9 [3.0-8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054-2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089-2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0-282) days compared to 312 (95% CI 195-428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019-3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.

Designing authentic simulations in ROSE and EBUS for undergraduate laboratory medicine students.

Introduction: Simulation-based education (SBE) has successfully been implemented in several healthcare professions, more so in the fields of medicine and nursing. Laboratory medicine courses prepare medical scientists for employment in pathology laboratories typically via a staged training regime. Laboratory techniques related to the diagnostic disciplines are introduced to students in a graduated fashion over time for the development of professional skills and technical competencies. For students specialising in diagnostic cytology, there are continual changes to the scope of practice of scientists in industry that require advanced training at undergraduate level to meet expectations of contemporary laboratory testing. Methods: The National Health Education and Training in Simulation (NHET-Sim) framework was applied to create and deliver bespoke simulations for laboratory medicine students. This paper outlines the steps taken, including working with actors and industry partners, to create simulations which contextualise the pressures and team interactions during diagnostic procedures. Findings: Supported by a range of expertise and personnel, five laboratory medicine simulations were developed and delivered to final year students. Details of the steps taken and range of scenarios are included for sharing and discussion. Discussion: SBE can contribute positively to student confidence in communication at interdisciplinary and interprofessional levels in ways that can be essential to successful patient management. Understanding that cytology has now evolved to become part of a multidisciplinary approach to patient-centred care will improve the overall patient outcome and experience to personalised medicine. Conclusion: This paper demonstrates how a high-fidelity SBE scenario can test students' decision-making around technical, clinical and diagnostic competencies in a complex investigation that they would likely experience in industry.

Manufactured Cell Blocks: Turning Smears into Sections.

Whilst cytological smears are still the basis of cytodiagnosis, there is an increasing role for ancillary testing. Specimens obtained are not always optimal, often with limited material for ancillary studies. Several reports have described the utility of scraping material from cytological smears to manufacture cell blocks to provide material for ancillary studies. Our objective was a retrospective review of the PathWest (QE2) experience with manufactured cell blocks (mCB) over the last 10 years. A total of 178 fine-needle aspiration cases with mCB were extracted from the PathWest database. Data were subdivided into: lymph node (89), breast (31), thyroid (23), soft tissue (13), liver (11), and other sites (11) and were analysed. All available material was reviewed. Diagnostic material was identified in 163 mCB (91.6%). Immunohistochemistry (IHC) was performed on 149 cases. Positive IHC staining was seen in 139 cases (93.3%) and advanced the diagnosis in 119 cases (79.9%). Molecular studies were performed on 38 mCB with adequate DNA obtained in 37 cases (97.3%). Our review has demonstrated that cellular material scraped from air-dried or prefixed smears can be made into cell blocks. Antigen preservation is adequate to provide diagnostically useful results with IHC whilst DNA integrity is preserved to allow molecular analysis.

The role of receptor for advanced glycation end products in airway inflammation in CF and CF related diabetes.

Cystic Fibrosis (CF) is often accompanied by diabetes leading to worsening lung function, the reason for which is unclear. The receptor for advanced-glycation-end-products (RAGE) regulates immune responses and inflammation and has been linked to diabetes and possibly CF. We performed a pilot study to determine if CF and CF-related diabetes (CFRD) are associated with enhanced RAGE expression. Full length (fl)RAGE, soluble (s)RAGE, endogenous soluble (es)RAGE, S100A12 (enRAGE) and advanced-glycation-end-products (AGE) expression was assessed in serum, white blood cells and sputum of patients with CF; diabetes; CFRD and healthy subjects. Sputum enRAGE/sRAGE ratios were high in CF but particularly in CFRD which negatively correlated with % predicted FEV1. Serum AGE and AGE/sRAGE ratios were high in diabetics but not in CF. A complex, multifaceted approach was used to assess the role of RAGE and its ligands which is fundamental to determining their impact on airway inflammation. There is a clear association between RAGE activity in the airways of CF and CFRD patients that is not evident in the vascular compartment and correlates with lung function, in contrast to diabetes. This strongly suggests a role for RAGE in contributing to the inflammatory overdrive seen in CF and to a greater extent in CFRD.

Predictive value of diagnoses of endocervical glandular abnormalities in cervical smears.

AIMS: To determine the positive predictive value (PPV) of cervical smear diagnoses of 'definite' and 'possible' endocervical adenocarcinoma in situ or invasive adenocarcinoma, and whether diagnostic accuracy can be improved. METHODS: The study examined cervical smears reported as definite or possible high-grade glandular abnormality between 1992 and 1998. PPV was calculated by comparing smear diagnoses with the subsequent histopathology report. All available smears were reviewed without knowledge of follow-up results, and were reclassified by consensus. RESULTS: Thirty-two smears were diagnosed as high-grade glandular lesions, with adequate biopsy follow-up in 31 cases (96.9%). A high-grade epithelial abnormality (HGEA) was detected in 29 cases (PPV, 93.5%), with a high-grade glandular lesion in 24 (PPV, 77.4%). Very few smears were reclassified on review. Seventy-three smears were initially diagnosed in the 'inconclusive' glandular or indeterminate cell-type category. There was adequate biopsy follow up for 54 cases (74.0%). On follow-up, 31 cases had a HGEA (PPV, 57.4%), with 14 cases having a high-grade glandular abnormality (PPV, 25.9%). In the review of 'inconclusive' smears, 12 were reclassified as squamous abnormalities and none of these had a glandular lesion on biopsy. Eight were reclassified as negative; seven contained endometrial stroma and the glandular cells in question were considered to be of lower uterine segment (LUS) origin. No significant lesion was present on follow-up of these cases. CONCLUSIONS: For clinicians using our laboratory, large loop excision of the transformation zone (LLETZ) or cone biopsy should follow a 'definite' cytological diagnosis of a high-grade endocervical glandular lesion. However, cone biopsy may not be the appropriate initial management in the 'possible' high-grade glandular group because of a significantly lower predictive value of the diagnosis. The slide review highlighted the importance of (1) caution in classifying sheets of abnormal cells as glandular, and (2) endometrial stroma as a marker of LUS material.

Adenocarcinoma in situ of the cervix.

BACKGROUND: The current study examines 1) the sensitivity of detection and 2) sampling and screening/diagnostic error in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix. The data were taken from public and private sector screening laboratories reporting 25,000 and 80,000 smears, respectively, each year. METHODS: The study group was comprised of women with a biopsy diagnosis of AIS or AIS combined with a high-grade squamous intraepithelial lesion (HSIL) who were accessioned by the Western Australian Cervical Cytology Registry (WACCR) between 1993-1998. Cervical smears reported by the Western Australia Centre for Pathology and Medical Research (PathCentre) or Western Diagnostic Pathology (WDP) in the 36 months before the index biopsy was obtained were retrieved. A true measure of the sensitivity of detection could not be determined because to the authors' knowledge the exact prevalence of disease is unknown at present. For the current study, sensitivity was defined as the percentage of smears reported as demonstrating a possible or definite high-grade epithelial abnormality (HGEA), either glandular or squamous. Sampling error was defined as the percentage of smears found to have no HGEA on review. Screening/diagnostic error was defined as the percentage of smears in which HGEA was not diagnosed initially but review demonstrated possible or definite HGEA. Sensitivity also was calculated for a randomly selected control group of biopsy proven cases of Grade 3 cervical intraepithelial neoplasia (CIN 3) accessioned at the WACCR in 1999. RESULTS: For biopsy findings of AIS alone, the diagnostic "sensitivity" of a single smear was 47.6% for the PathCentre and 54.3% for WDP. Nearly all the abnormalities were reported as glandular. The sampling and screening/diagnostic errors were 47.6% and 4.8%, respectively, for the PathCentre and 33.3% and 12.3%, respectively, for WDP. The results from the PathCentre were better for AIS plus HSIL than for AIS alone, but the results from WDP were similar for both groups. For the CIN 3 control cases, the "sensitivity" of a single smear was 42.5%. CONCLUSIONS: To the authors' knowledge epidemiologic studies published to date have not demonstrated a benefit from screening for precursors of cervical adenocarcinoma. However, in the study laboratories as in many others, reasonable expertise in diagnosing AIS has been acquired only within the last 10-15 years, which may be too short a period in which to demonstrate a significant effect. The results of the current study provide some encouraging baseline data regarding the sensitivity of the Papanicolaou smear in detecting AIS. Further improvements in sampling and cytodiagnosis may be possible.

Comparison of a recombinant-antigen enzyme immunoassay with Treponema pallidum hemagglutination test for serological confirmation of syphilis.

A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN anti-Treponema pallidum, was compared favorably with the T. pallidum hemagglutination test, in the detection of specific antibodies in different groups of sera from patients with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n = 13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant women (n = 29) and blood donors (n = 164). The coincidence between them was 95.1%. The sensitivity and specificity of the EIA were 93.3% and 95.5%, respectively. Fifteen serum specimens belonging to old-persons, pregnant women, blood donors, and patients with human leptospirosis, hepatitis, diabetes mellitus, tuberculosis and rheumatic fever gave false-positive results by Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be used as alternative method for the serological confirmation of syphilis.

Comparison of a Recombinant-antigen Enzyme Immunoassay with Treponema pallidum Hemagglutination Test for Serological Confirmation of Syphilis

A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN TM anti-Treponema pallidum, was compared favorably with the T. pallidum hemagglutination test, in the detection of specific antibodies in different groups of sera from patients with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n = 13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant women (n = 29) and blood donors (n = 164). The coincidence between them was 95.1 percent. The sensitivity and specificity of the EIA were 93.3 percent and 95.5 percent, respectively. Fifteen serum specimens belonging to old-persons, pregnant women, blood donors, and patients with human leptospirosis, hepatitis, diabetes mellitus, tuberculosis and rheumatic fever gave false-positive results by Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be used as alternative method for the serological confirmation of syphilis