Meeting the needs of modern pathology services

At two meetings hosted recently by Roche Diagnostics in central London, delegates learned how developments in diagnostic technology and processes are helping modern pathology services meet clinical and operational needs. Here we catch up with what was discussed

Dr Mark Atkins, Consultant Virologist at the Imperial College Healthcare NHS Trust, London, gave an overview of serology testing explaining how the discovery of new illnesses, together with the demand for screening for certain diseases and the monitoring of treatment/vaccine responses have driven new technologies in infectious disease diagnosis. The improvements in the quality, speed, reliability and turnaround time of tests now mean results can be obtained in hours rather than days, resulting in better patient management.

Focusing on the development of HIV testing, Dr Atkins explained that early diagnosis of primary infection is extremely important as patients are highly infectious during this phase. As the sensitivity and reliability of 4^th generation HIV tests have improved, infection can now be detected very soon after it has been contracted allowing swift treatment to greatly improve long term disease management and outlook for patients. 

Personalised healthcare for Hepatitis B Recent advances in management and treatment of chronic hepatitis B (CHB) based on quantitative hepatitis B surface antigen (HBsAg) measurements were discussed by Dr Patrick Kennedy, Senior Lecturer in Hepatology and Honorary Consultant Gastroenterologist and Hepatologist at Barts and The London NHS Trust. He explained how the loss of HBsAg is now considered the optimal goal of treatment strategies, representing the only surrogate marker of successful immunological control, and is associated with a lower incidence of cirrhosis and hepatocellular carcinoma (HCC), and improved survival. For this reason, treatment options for CHB (interferon and nucleos(t)ide analogs) are being re-evaluated in the context of their ability to result in HBsAg loss.

It has been demonstrated that a finite course of Pegylated Interferon (48 weeks) can result in HBsAg loss in a proportion of patients¹ and delivers a sustained immune control in 31% of patients². The demonstration of on-treatment HBsAg decline enables relapsers and non-responders to be distinguished from responders to interferon treatment³. The availability of on-treatment HBsAg quantification to monitor response to interferon treatment, therefore, provides the vehicle for an individualised approach to the management of chronic HBV, allowing those who are likely to achieve sustained immune control to be identified at an early stage.

Platform consolidation Sharing her experiences in the consolidation of serology assays onto an automated clinical chemistry and immunoassay platform was Jayne Harwood, Team Manager for Serology at the Newcastle upon Tyne NHS Foundation Trust. Jayne explained that seventeen serology assays

are used on the automated track system at Newcastle which includes a Pre-Analytics module (Roche MPA) and two lines with clinical chemistry (MODULAR ANALYTICS EVO <P>) and immunoassay (MODULAR ANALYTICS EVO <E>) analysers. She said that this platform consolidation, which is part of a Managed Laboratory Service agreement, has improved serology result turnaround times, reduced staffing requirements and given a reduction in operational costs (with fewer repeat tests and controls required).

Diagnosis and management of ToRC Dr Liliane Grangeot-Keros, Pharmacist and Associate Professor in Virology, Antoine Beclere Hospital, France described developments in the diagnosis and management of ToRC (toxoplasma, rubella and CMV) infections. During pregnancy, ToRC infections can be transmitted to the fetus, so determination of immune status can be proposed in order to give hygiene counseling during pregnancy (CMV infection and toxoplasmosis) or to immunize seronegative women after delivery (rubella).

Diagnosis of primary maternal ToRC infection is mainly based on serology, however results can be difficult to interpret and misinterpretation may have serious consequences. Dr Grangeot-Keros described a wide variation in result sensitivities across assays from different manufacturers and stressed the importance of comparing results from the same laboratory, using the same assay, for meaningful interpretation.

New infectious disease markers Dr Roland Hofweber, Study Manager Clinical Operations for Roche Diagnostics then described important new or forthcoming Roche infectious disease markers including a new quantitative HBsAgII assay and a new CMV IgG avidity test, launched earlier this year, as well as a new anti-hepatitis C virus assay and a Toxoplasmosis avidity test which will be available shortly.

The “Focus on Serology” day was chaired by David Frodsham, Directorate Manager of Pathology and Acting Associate Director for Clinical Support Services at the University Hospital of North Staffordshire NHS Trust.

Focus on driving efficiencies Dr Martin Myers, Consultant Chemical Biochemist and Clinical Director at Lancashire Teaching Hospitals NHS Foundation Trust, chaired day two of the event where speakers shared visions for innovative diagnostic solutions that will drive efficiencies whilst maintaining quality.

Steve Graham, Innovative Technology Adoption Procurement Programme (iTAPP) Lead for the Department of Health described the work of iTAPP and the invitations extended, via trade organisations, to technology manufacturers to present their cases for adoption of specific testing techniques within the NHS. He gave examples of iTAPP interest in nearly 60 technologies that represent the best opportunity to realise the earliest benefits and described progress towards adoption of these technologies.

Harmonisation of cardiac biomarkers Dr Myers reviewed some of the clinical (e.g. the formation of clinical networks and NICE guidelines) and political (e.g. the Carter report and Pathology QIPP) drivers for harmonisation.  For accreditation purposes, it is important to have traceability and a reduction in uncertainty.  Harmonisation requires agreement on test names, units, reference ranges, formulary of tests and interpretation of results. There needs to be a standardization of services, Dr Myers stressed, in order to reduce confusion and ‘postcode’ biochemistry.

He described recent consensus thoughts in the use of the cardiac biomarkers, troponin T high sensitive (TnT hs) and natriuretic peptides (NTproBNP), based on NICE and other recent guidelines^4-9. He concluded that there is an opportunity to harmonise the use of these biomarkers across the UK, rather than have multiple local interpretations, it would be better to harmonise on best evidence and review when appropriate.

Total vitamin D testing Vitamin D plays a central role in calcium and phosphorus metabolism and skeletal health. It has recently been recognised that many individuals, both children and adults, have a relative insufficiency or mild deficiency of vitamin D, which may point to metabolic bone disease or other conditions, such as cardiovascular disease, pre-eclampsia and multiple sclerosis.

Two representatives from the Biochemistry Department at the Queen Elizabeth Hospital (QEH) Gateshead NHS Foundation Trust, John Fenwick (Technical Manager) and Hayley Richardson (Specialist Biomedical Scientist), presented the benefits of consolidating total Vitamin D testing onto an automated immunoassay system. The Roche Elecsys Vitamin D total assay was evaluated at the QEH and it performed well compared to their existing semi-automated method.  This automated assay has allowed the laboratory to bring vitamin D testing in-house, extending their test menu and significantly improving turnaround test times.

Automated HbA1c testing The next presenter described experiences of diabetes testing using the Roche Tina-quant HbA1c assay in an extensive main hospital, regional hospitals and clinic setting. Dr Sihe Wang, Section Head for Clinical Biochemistry at the Cleveland Clinic Hospital in Ohio, USA, described how the main hospital campus and its seven regional hospitals received a total of 4.2 million patients visits, and processed 30 million individual tests – figures that staggered the UK audience!

Focusing on the effect on laboratory turnaround times and the benefits of automating HbA1c testing, Dr Wang reported that the assay is easy to use, meets the College of American Pathologists Proficiency Testing (CAP PT) standards, and gave comparable results when compared to a commercial HPLC assay and allowed detection of anaemic patient samples. He also highlighted the NGSP study (http://www.ngsp.org/interf.asp) that recorded that Roche Tina-quant HbA1C assay showed no interference from HbAS, HbAC, HbAD,HbAE, and other haemoglobin variants. He advised that consolidation onto Roche automated platforms helped to improve turnaround times and result consistency across all the laboratories in the Cleveland Clinic campus and they are now able to offer a 24/7 service.

Improvements in ovarian cancer diagnosis Concluding the seminar days, Dr Achim Escherich, Senior International Product Manager (Oncology) for the Roche Global Assay Development Team described the novel dual marker combination, Elecsys HE4 (human epididymal protein 4) and CA 125 II, and their use in supporting improvements in ovarian cancer diagnosis and therapy in women with pelvic mass.

As a single tumor marker, HE4 has the highest sensitivity and specificity for detecting ovarian cancer¹⁰. Applying the two independent markers (CA 125 and HE4) together, the risk estimation of epithelial ovarian cancer in women presenting with pelvic mass can be further improved. The dual marker combination yielded the highest sensitivity, especially in the early, nonsymptomatic stages of ovarian cancer, and reduces the percentage of biomarker-negative ovarian cancer by 30-50%¹¹.

References

1. Reijinders JGP, et al. European Association for the Study of the Liver (EASL) 2010; Poster #1021.
2. Marcellin P, Piratvisuth T, Brunetto M, et al. (2010) On-Treatment Decline in Serum HBsAg Levels Predicts Sustained Immune Control 1 Year Post-Treatment and Subsequent HBsAg Clearance in HBeAg-Negative Hepatitis B Virus-Infected Patients Treated with Peginterferon Alfa-2a [40KD] (PEGASYS).  Poster presentation at the Asian Pacific Association for the Study of the Liver (APASL) conference 2010
3. Moucari R, MackiewiczV, LadaO et al (2009)  Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients Hepatology 49 (4) 1151-1157.
4. Thygesen K, Alpert JS, and White HD. (2007)  Universal Definition of Myocardial Infarction. J Am Cardiol. 50: 2173–95
5. NICE Guideline 95. Chest pain of recent onset: Assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. 2010
6. Thygesen K, Mair J, Katus H et al. (2010) Recommendations for the use of cardiac troponin measurement in acute cardiac care. European Heart Journal 31: 2197–2206
7. NICE Clinical Guideline 108.  Chronic heart failure Management of chronic heart failure in adults in primary and secondary care
8. Hildebrandt P, Collinson PO, Doughty RN, et al. (2010) Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care. European Heart Journal  31:1881–1889.
9. Thygesen K, Mair J, Mueller C et al.  (2011) Recommendations for the use of natriuretic peptides in acute cardiac care. European Heart Journal 2011 in press
10. Coukos G, Berchuck A and Ozois R (eds) (2008) Ovarian Cancer (Springer 2008)
11. Moore RG, Brown AK, Miller MC, et al. (2008) The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 108:402-408