2016 4 s Newsletter

Test updates 3 Health changes to affect us all 4 Gilbert’s syndrome 6 Inside World Pathology Day 7 Urinary Free Cortisol 8 DOACs and coagulation assays 10 Mesothelioma research 10 What is PSA? 12 Berri Victor Harbor Gawler Flinders Medical Centre Port Augusta Lyell McEwin Hospital Murray Bridge Port Pirie Wallaroo QEH Port Lincoln Noarlunga Whyalla WCH Mount Gambier For our patients and our population www.sapathology.sa.gov.au From the inside new systems work as training and testing become part of our daily routines during transition.

Getting major analyser track systems and standalone instruments to interface with intelligent software will take time as each part of the service network comes online. Patient management and information systems must align, ensuring that data is kept secure but readily accessible to clinicians. All this takes place concurrent with Group & Hold tests physical relocation to the new RAH and equipment upgrades to all laboratories, Clinicians are reminded that patients while maintaining our quality of service requiring Group & Hold (G&H) blood and current turnaround times. tests need to have blood taken within seven (7) days of their scheduled While it will present unique challenges surgery. for staff, we have planned extensively for sa pathology , 2016 will be to ensure we manage this effectively. a year of technical, logistical and Patients who have been transfused We have allocated significant resources business challenges. We are acutely in the preceding three months, who to our laboratory information system aware of the pressures involved in are currently pregnant – or have been involving scientists and technical completion of SA’s new hospital and the pregnant in the previous three months experts, who have devoted their energies flow-on effect for us, coordinating key to building and testing processes which – must have their G&H tests performed clinical support services and ICT and will ultimately achieve full integration within three (3) days of scheduled analytical processes. across one state-wide network. surgery. The complexity in aligning patient As SA Pathology embraces this major ECG bookings information across the state, from organisational change, we continue to country hospitals to large medical If your patient needs an ECG in addition adhere to the highest standards centres, is significant, as are the to their blood test a booking is required of scientific and clinical excellence as technical aspects of building, testing for the ECG. SA’s public pathology provider to health. and implementing the most advanced automated pathology system in the Professor Robert Heddle To make an appointment please phone world. It will require adapting to how ACTING EXECUTIVE DIRECTOR Enquiries on (08) 8222 3000. ¥

SA Pathology Newsletter Published by SA Pathology New Patient Centres Editorial Committee Mark Fitz-Gerald, Dianne Zurcher, Kieran Weir Belair Semaphore and Adrian Griffiths 459 Belair Road, Belair 108A Semaphore Road, Semaphore Contact [email protected] (located in the Belair Family Health (located in the Spring Life Medical Photography Centre) Centre) SA Pathology Photo and Imaging Tuesdays and Fridays Mondays and Fridays Design from 8.00am to 11.00am from 8.00am to noon Sue Dyer Design Printing Two Wells Newstyle Printing Cover 32 Mallala Road, Two Wells We’re installing new analyses in all our (located in the Two Wells Medical Clinic) Please check laboratories statewide – see page 4 for more Mondays, Tuesdays and Thursdays www.sapathology.sa.gov.au on this story. from 9.00am to noon for the latest opening hours ISSN 2203 – 2339 Print ISSN 2203 – 2347 Online

SA Pathology Newsletter > 4 – 2016 PAGE 2 TEST UPDATES

Trichomoniasis – Nucleic Acid Who to test More about TV Testing (NAT) n Symptomatic women with Trichomoniasis is a sexually- vaginitis or vaginal discharge transmitted disease caused by the SA Pathology now uses a Nucleic protozoa Trichomonas vaginalis. n HIV-positive women on entry Acid Test (NAT) for Trichomonas Whilst not common in urban Australia to care and at least annually vaginalis (TV) detection and promotes it occurs in certain high-risk groups thereafter targeted testing in symptomatic including indigenous communities. patients and high-risk groups. NAT n consider screening asymptomatic is asymptomatic in 70-85% is more convenient as it is performed high-risk populations (e.g. STD of cases and occurs in the vagina, on the same specimens as APTIMA clinic patients) and other groups vulva, and female and male urethra. gonorrhoea and chlamydia tests. depending on local epidemiology; Sensitivity and specificity are also and Further information greatly increased. n male patients if initial Please phone Enquiries on investigations for urethritis (08) 8222 3000 and ask for the If TV testing is required TV NAT are negative. On Call Microbiologist. ¥ must now be specified on the pathology request. RCO reference interval change For patients with suspected cortisol excess, 24 hour urinary SA Pathology changed to a free cortisol or midnight salivary new method of cortisol (RCO) cortisol screening is recommended. measurement which has lower For example, pregnant women and cross reactivity than the previous women taking oral contraceptives method, and is traceable to the latest often have high morning cortisol international reference standard. levels, due to increased production of cortisol binding globulin. Because of the lower cross reactivity with native and synthetic Further information corticosteroids, patient cortisol Please phone Enquiries on results are up to 20% lower with (08) 8222 3000 and ask for the the new method, hence both the On Call Biochemist. ¥ reference range and the targets after Synacthen stimulation have changed. What to collect In addition to the usual swab for New reference intervals bacterial culture, please send a second RCO (Random Cortisol) at 0900h 133 – 540 nmol/L specimen using the APTIMA collection SST (Short Synacthen Test) – Normal >450 nmol/L in at least one kit as for gonorrhoea and chlamydia. 30 or 60 minutes post stimulation sample A first-void urine specimen may also be used.

SA Pathology provides a range of useful Quick Guides and many have recently been updated. To re-order simply call Consumer Products on (08) 8222 3394 or ask your Business Development Officer when next they call.

Infectious Disease Tests Order of Draw Urine / Genital / Skin Surgery Guide Regional Hospitals PUB – 0073 v4 PUB – 0085 v7 PUB – 0483 v1 Blood / Respiratory / Enteric Metropolitan Hospitals Specimen Collection & Labelling PUB – 0064 v4 PUB – 0004 v7 PUB – 0549 v1 Guides Quick

SA Pathology Newsletter > 4 – 2016 PAGE 3 www.sapathology.sa.gov.au Health changes to affect us all SA Pathology was created eight years ago with the amalgamation of the IMVS, the Women’s and Children’s Hospital (WCH) and Flinders Medical Centre (FMC) laboratories. Since then much has been achieved by introducing common systems and consolidating methods. In the next eighteen months, as the new Royal Hospital (new RAH) opens its doors and we install state of the art pathology analysers and IT systems, we will complete one of the most ambitious and sophisticated upgrades since the introduction of automation.

Worldwide, medicine is undergoing radical structural change and it is affecting us all. The changes flow from the intersection of advances in automation, computer technology and electronic communication systems, coupled with significant leaps in scientific understanding and medical practice, notably in the field of genetics.

Late last year, SA Pathology became the first Australian pathology laboratory accredited to offer patients in clinical need access to new methods of diagnosis which New standards – we’re installing new analysers in all our regional labs too can examine 20,000 human genes in a single test (see SA Pathology The healthcare revolution Newsletter Issue 3). The South Australian government Introduction of interlinked systems has set the scene for change with will have implications for all tiers the construction of the new RAH and of service delivery, from hospitals to its Transforming Health initiatives. the local GP. Coded at the time of The technological innovations on collection, there will be fewer manual which the new hospital relies also tasks in reception, ensuring that provide real opportunities to improve when specimens arrive they will be the clinical and laboratory workflow routed to the right analysers faster. for SA Pathology. The chance of mislabelling or lost samples will be reduced even further. The introduction of a new electronic Adding on tests will be easier because patient administration system, linked we will know where each tube is in to a single state-wide pathology the workflow and how much sample laboratory information system will remains available to test. revolutionise the flow of information and how pathology tests are ordered The new streamlined approach, based and reported. Individual tests will be on common analysers across the state Staff and installers with the microbiology track more visible and trackable, showing will increase our efficiency, improve taking shape at the new RAH progress and results more readily. communication and reduce cost.

SA Pathology Newsletter > 4 – 2016 PAGE 4

New RAH SA Pathology will be integral in the on identical test platforms. The operations of the new Royal Adelaide standardisation will ensure result Hospital. In our soon to be occupied consistency and interpretation. laboratories, we are constructing one of the most sophisticated automated To achieve this, we must run parallel track systems available. Ultimately systems during the transition to there will be over 150 analysers accommodate legacy equipment and directly connected to new intelligent software. scheduling, ordering and reporting software. These new automated At SA Pathology we are embracing systems will transform the capacity these initiatives as a once-in-a- of pathology and provide seamless generation opportunity to build a integration in critical hospital better service. As with any change of workflows. this magnitude, there will be flow-on Future focus effects for hospital staff, clinicians We will consolidate our primary and general practitioners; we will all Our presence in the new hospital critical care service into the new RAH, be doing things differently and will is only one part of our future; retaining less urgent operations at be working with doctors to ensure inside SA Pathology we are actively our Frome Road laboratories. Whilst all their clinical requirements are embracing the notion of change. presenting logistical challenges during fully supported during the transition When all the necessary IT the transition phase, this evolution period. projects are completed and represents major opportunities, and communications systems linked the long-term benefits to health Benefits with our analysers, we will realise professionals, to our organisation Clinicians in regional centres additional benefits as further and the wider community, cannot be whose patients require care in city integration with robotics and underestimated. hospitals will benefit from this unified automated track systems become approach. the new standard. Across the state Whilst the initial impact of these The new RAH is a substantial project Other benefits include operational major initiatives will be felt first for SA Pathology, but change consistency across our organisation, in public hospitals, eventually extends further. We have also with workflows and training the benefits will flow to health embarked on a state-wide equipment standardised in all laboratories, professionals everywhere. This upgrade, due for completion in creating a ‘common conversation’ is a momentous era globally for June 2016, which will see the same for all staff and giving them medicine and we will be there to haematology and biochemistry confidence in identical methods, support the clinicians of South analysers installed in all our regional wherever they work. The outcome Australia as change envelops and metropolitan laboratories, the for clients is that we will be able to us all. first of which was installed recently offer the same informed responses at Modbury Hospital. When all the to technical and clinical questions, These promise to be challenging equipment has been installed, no regardless of location. and exciting times and matter where tests are ordered, SA Pathology will be working whether in the Fleurieu, Yorke or with you to ensure patients remain Eyre peninsulas, or Riverland, South at the centre of care, now and in East or metropolitan areas, clinicians the future. ¥ will receive results generated

SA Pathology Newsletter > 4 – 2016 PAGE 5 www.sapathology.sa.gov.au

Gilbert’s syndrome Dr Mohamed Saleem

Gilbert’s syndrome was first described at the turn of the twentieth century by Nicolas Augustin Gilbert and Pierre Lereboullet who reported a syndrome of benign, periodic jaundice occurring without any other symptoms of liver disease. Sometimes called ‘constitutional hepatic dysfunction’ or ‘familial benign unconjugated hyperbilirubinaemia’ the names reflect important clinical aspects of the condition which affects bilirubin conjugation by the liver resulting in increased blood bilirubin concentration, most of which is unconjugated.

In Australia, the prevalence of this others, especially in situations where syndrome is reported to be between bilirubin load is increased or bilirubin 2 and 5% and has no significant clinical metabolism is altered. consequences. However, appropriate Elevated levels usually first appear diagnosis is important to prevent during adolescence, when alterations further unnecessary and/or invasive in sex steroid concentrations alter investigation. bilirubin metabolism. Occasionally Pathophysiology mild jaundice may be noticed; however patients with Gilbert’s Gilbert’s syndrome is often an syndrome do not have pruritus, inherited condition caused by dark urine or pale stools which are decreased hepatic levels of the enzyme typical of obstructive jaundice. glucuronosyltransferase (UGT) which is responsible for the conjugation There is some evidence to suggest of bilirubin in the liver. Decreased that individuals with Gilbert’s enzyme activity leads to decreased syndrome may be at higher risk

conjugation of bilirubin and subsequent Nicolas Augustin Gilbert accumulation of unconjugated bilirubin in the circulation. The most important aspect of diagnosis The genetic defect has been identified is recognizing the disorder without as the presence of two additional nucleotides in the gene encoding subjecting patients to invasive or UGT, leading to reduced gene expression and therefore reduced unnecessary testing production of the UGT enzyme. fever, infection or intercurrent of toxicity from medications, Gilbert syndrome manifests only in disease, menses, excessive exertion including some anticancer drugs and people who are homozygous for the or alcohol consumption. paracetamol, which are metabolised variant and therefore its inheritance in the liver, compared with unaffected is most consistent with an autosomal Clinical findings individuals. Hence, they may be more recessive trait. In affected individuals prone to toxicity after paracetamol enzyme activity is usually 25-30% of Classically Gilbert’s syndrome overdose. normal levels. presents as an incidental finding of isolated mildly elevated bilirubin Diagnosis Commonly, in people with Gilbert’s (25-40umol/L) in a set of liver syndrome, the level of bilirubin is function tests. Although bilirubin A test request for conjugated slightly elevated at all times, and may results within the reference interval bilirubin (fractionation) can be be further increased in situations may occur in some individuals, results useful in establishing unconjugated such as starvation, effects of surgery, as high as 80umol/L may be seen in hyperbilirubinaemia.

SA Pathology Newsletter > 4 – 2016 PAGE 6

A presumptive diagnosis of Gilbert’s syndrome can be made based on mildly elevated unconjugated bilirubin WORLD PATHOLOGY DAY (usually provoked by factors such as those mentioned previously) with no Pathology is a critical part of modern clinical practice with over other liver function test abnormalities. 70% of diagnosis relying on the results of pathology tests. This year we celebrated World Pathology Day with patients and their families As the main differential diagnosis for at the Women’s and Children’s Hospital. an elevated unconjugated bilirubin is haemolysis, a full blood examination SA Pathology staff answered and reticulocyte count may be useful questions about pathology and to exclude haemolysis as a cause. provided demonstrations for The diagnosis is definitive in patients the public with a multi-headed who continue to have normal microscope using blood smears, laboratory studies (other than mild showing how conditions like malaria unconjugated hyperbilirubinaemia) are recognised and demonstrating over 12 to 18 months. techniques in diagnosis of haemophilia. Management The interactive displays and As there is no increased morbidity discussions proved popular with or mortality associated with this those who took the time to look condition, no specific treatment is ‘behind the scenes’ at the science required. Except for an increased which touches many of their lives on incidence of side effects from certain a daily basis, considering many of drugs the most important aspect those we spoke with at the hospital of the care of these patients is have children with ongoing health recognition of the disorder and its issues. inconsequential nature. Its mode of inheritance should also be discussed SA Pathology’s Executive Director to prevent unnecessary testing in said the purpose of the day was to family members. make activities for World Pathology SA Pathology medical scientist Day engaging and educational for Samantha Reardon, our public face for people of all ages. World Pathology Day at WCH More about Gilbert’s syndrome Malaria parasite p falciparum Gilbert’s syndrome is caused by an abnormal inherited gene and is more common in males. Normally Sickle cell anaemia the gene controls an enzyme that helps break down bilirubin in the liver. Bilirubin is produced when the body breaks down ageing red blood cells; an ineffective gene leads to reduced levels of enzyme and hence excess amounts of bilirubin build up in the blood, its yellowish colour producing the mild jaundice characteristic of the syndrome. Malaria parasite p vivax Whilst the abnormal gene that causes Gilbert’s syndrome is common (many people carry one “It’s about more than an opportunity to simply copy), two abnormal copies are promote SA Pathology; it’s us informing the public generally required. about the value of pathology generally, exposing Although present from birth, the people to the various disciplines within pathology syndrome is usually not noticed until puberty or later, when bilirubin and highlighting the essential service we offer production increases. ¥ doctors and patients.”

SA Pathology Newsletter > 4 – 2016 PAGE 7 www.sapathology.sa.gov.au

Urinary Free Cortisol 6am 9am 12pm 3pm 6pm 9pm 12am 3am 6am

Andrew Fudge

At SA Pathology we recently changed our method for Urinary Free Cortisol (UFC) and now use Liquid Chromatography Tandem Mass Spectroscopy (LC-MSMS) which is specific for cortisol. Because non-active steroids in urine are not measured with this method, the reference interval is about half of the range of the previously used immunoassay. The advantages of LC-MSMS assays for UFC testing are well documented and have been accepted as the ‘gold standard’. UFC is predominately used in the investigation of Cushing’s syndrome.

Cortisol Figure 1 Commonly Cushing’s syndrome is caused by the use of corticosteroid Cortisol’s functions include regulation medication in the treatment of of blood sugar and blood pressure, Hypothalmus inflammatory conditions such as fighting infection, mood regulation asthma and arthritis. It may also result and the metabolism of carbohydrates, from a tumour that either directly or fats and proteins. CRH indirectly causes excessive cortisol Negative production by the adrenal glands. Variation feedback Cases due to a pituitary adenoma are Cortisol is synthesised from known as Cushing’s disease. cholesterol in the adrenal cortex. Anterior pituitary This is stimulated by pituitary Symptoms adrenocorticotrophic hormone As glucocorticoids such as cortisol (ACTH). ACTH is stimulated by ACTH have such widespread effects on both corticotrophin-releasing hormone metabolism and the immune system (CRH) from the hypothalamus and the signs and symptoms of CS can inhibited by cortisol, and hence Adrenal cortex be difficult to attribute. They include controlled by negative feedback sudden weight gain around the (see figure 1). ACTH release, and abdomen, obesity, facial plethora, a consequently cortisol secretion, ‘buffalo hump’ of fat high on the back, is stimulated by physical and thin skin that easily bruises and slow mental stress. Cortisol healing ulcers, impotence, hirsutism, menstrual disorders, hypertension, Cortisol follows a circadian rhythm violaceous striae, increased thirst in healthy people. It is highest and urination and headache. between 6am-8am, and falls High concentrations of biologically Opportunistic or bacterial infection throughout the day to reach a active unbound cortisol are may complicate the presentation. minimum level during sleep. responsible for the signs and symptoms of hypercortisolism. The non-specific nature of many symptoms means that diagnosis must Most cortisol circulates bound to be confirmed by biochemical analysis. cortisol-binding globulin and albumin. Cushing’s syndrome Normally less than 5 percent of Cushing’s syndrome (CS), also known Diagnosis circulating cortisol is the unbound as hypercortisolism, is a collection Cushing’s syndrome can be (free) and physiologically active of symptoms caused by prolonged categorised as ACTH dependent form. Free cortisol is filtered by the exposure to high levels of cortisol. or ACTH independent. ACTH renal glomerulus which is why plasma It usually presents between 20 and dependent includes Cushing’s disease, cortisol levels correlate well with 50 years of age and is more prevalent Ectopic ACTH syndrome and Ectopic UFC levels. in women. CRH syndrome.

SA Pathology Newsletter > 4 – 2016 PAGE 8

ACTH independent can include Laboratory testing iatrogenic causes and adrenal The urine free cortisol test measures AWARDS AND adenoma. This division is convenient the total amount of cortisol excreted ACHIEVEMENTS for organising the work-up of patients into the urine over a 24-hour period. with suspected CS which should It is not affected by conditions which 2015 was a very successful year include: increase cortisol binding proteins for SA Pathology initiatives and such as pregnancy or the oral n a medications review collaborations. Patient centred contraceptive pill. care and continuous improvement n measurement of cortisol levels in of our processes and service are a 24-hour urine or midnight saliva The Endocrine Society’s Clinical central to what we do. specimen, or in blood after taking Practice Guidelines recommend Best practice ordering dexamethasone screening for CS using either: Unnecessary or inappropriate n Morning random cortisol is n 24 hour urinary free cortisol ordering of pathology tests increases usually not helpful in investigating measurement (UFC) cost and turnaround times and suspected hypercortisolism. consumes valuable resources. n a late night salivary cortisol Cortisol is normally at its highest at Having recognised this, staff at this time, and increases further in (LNSC) or Southern Adelaide’s Local Health many patients even with the stress n a 1 mg Dexamethasone Suppression Network (SALHN) collaborated with of blood collection. Test (DST) SA Pathology to improve pathology ordering in Flinders Medical Centre. n ACTH should only be measured A recently published examination of Incorporated into their professional after confirming hypercortisolism. development program, it was very screening tests concluded that UFC, This is because ACTH is highly successful and earned the SALHN when measured by LC-MSMS could variable during the day and normal team the major accolade in the SA individuals may have very high and be used as the primary screen for CS Health Awards ‘Enhancing Hospital very low ACTH levels within a few due to its high sensitivity; and that the Care’ category. We congratulate them minutes of each other. 1 mg DST should be performed only on their initiative and winning this in patients with high UFC levels. award. Awards It is important to bear in mind that As we reported in SA Pathology the guidelines recommend two Newsletter Issue 2 and following 24 hour urine samples be obtained many years of work by staff, our Rounded for diagnosis. Another recent study of BloodMove strategy, which achieved face patients with persistent or recurrent significant savings and minimised loss Cushing’s disease showed that within- of precious blood donations at sites patient variability of UFC can be as throughout , won the high as 50 percent which reinforces ‘Non-Clinical Service Deliver’ award the need for repeat samples. at the annual Australian Council on Healthcare Standards (ACHS) Quality Improvement Awards. What to collect A 24 hour urine collection in a plain container is preferred however, a sample collected with HCl is ‘Buffalo’ hump acceptable. Creatinine is reported as an indicator of the completeness of the urine collection. If clinical suspicion is high, a second collection may be required to rule out cyclical Thin skin Cushing’s syndrome. easily bruises Further information At the SA Health Awards in November Please phone Enquiries on SA Pathology’s Genetics and (08) 8222 3000 and ask for the Molecular Pathology Laboratory won Violaceous On Call Biochemist. ¥ the ‘Excellence in Non-Clinical Service’ striae category as the first laboratory nationally accredited to examine 20,000 human genes in a single test, a significant achievement in patient care. See the SA Pathology Newsletter Issue 3 for more on this story.

SA Pathology Newsletter > 4 – 2016 PAGE 9 www.sapathology.sa.gov.au DOACs and coagulation assays dr simon McRae

Routine blood testing for therapeutic monitoring has long been an accepted component of anticoagulant therapy and was required due to the inter-individual variation in response and narrow therapeutic window of the traditional anticoagulants warfarin and heparin. Patient dissatisfaction with the need for regular blood monitoring was a major driving force in the development of the direct oral anticoagulants (DOAC).

Dabigatran (a direct thrombin All have demonstrated similar efficacy drug assays may be useful. All of inhibitor), rivaroxaban and apixaban and safety to previous standards. the DOACs have a relatively short (direct factor-Xa inhibitors) are DOACs half-life (7 to 14 hours) hence the To avoid misinterpretation of results currently PBS listed for the treatment timing of sample collection from the it is useful for clinicians to understand of non-valvular atrial fibrillation, with last dose of the agent should always the effect of DOACs on routine the latter two agents also available for be taken into account. anticoagulation assays and also the treatment of venous thrombosis. clinical scenarios in which requesting

Table 1 – DOAC impact on routine anticoagulation even when high levels of drug are present; hence normal results cannot aPTT PT TT be used to exclude the presence of Dabigatran + –/+ ++ this agent. Rivaroxaban – + – Apixaban – – – Measuring DOAC levels + prolonged – unaffected –/+ may or may not be prolonged Assays are available for the measurement of dabigatran (by a modified TT test known as the Impact on routine results INR levels greater than 2.0 should also raise suspicion that drug levels Haemoclot assay) and rivaroxaban Table 1 summarises the considerable may be high. and apixaban (by an anti-Xa based variation each of the DOACs have on assay). All are performed on a routine coagulation results. Rivaroxaban standard citrated sample (blue top). The PT is the assay most sensitive to Dabigatran rivaroxaban with INR results of 1.5 to It is emphasised that routine The thrombin time (TT) is the 2.0 commonly seen at peak levels. INR monitoring of these agents is not most sensitive assay for dabigatran, ; however, measuring the results of greater than 3.0 should raise required with a normal result excluding the DOAC level may be of use in certain the suspicion of drug excess, or an presence of the drug. The activated clinical situations. alternative cause of INR prolongation partial thromboplastin time (aPTT), An accurate (e.g. vitamin K deficiency). As like the TT, is usually prolonged estimate of drug rivaroxaban has low trough levels, by dabigatran, and a normal aPTT level can normally normal INR results can also be seen. generally excludes high drug levels. be made if the time The aPTT is only mildly prolonged Excessive prolongation of the aPTT of the last dose and by rivaroxaban unless high levels are is uncommon, and an aPTT at trough the patient’s renal present; TT, on the other hand, is of greater than 65 seconds or greater function are known. normal in the presence of rivaroxaban. than 80 seconds at any time should raise the suspicion of excessively Apixaban high drug levels. Prothrombin time All routine coagulation assays (aPTT, (PT) is not significantly prolonged by PT and TT) are insensitive to apixaban therapeutic levels of dabigatran and and therefore normal results are seen

SA Pathology Newsletter > 4 – 2016 PAGE 10 Research to help mesothelioma patients Mesothelioma, a malignant system, but insufficient levels reach tumour of the lung surface related the lungs so researchers hypothesised to inhalation of asbestos, can take that putting higher doses of curcumin 10 to 40 years to manifest in those directly into the pleural space may be who contract it. more beneficial. Scenarios in which measuring drug level may be of use include: Patients develop fluid build-up on Therapy the lungs which causes shortness Pleurodesis, still the most common n Active bleeding of breath and is extremely distressing. therapy available, is a surgical Is drug present in excess, or is Prognosis is extremely poor and most procedure where talc, instilled into therapeutic anticoagulation due to patients die within twelve months the pleural cavity, induces a foreign a DOAC contributing to the of diagnosis. Current treatments, body reaction which fuses the lung bleeding? including aggressive surgery and surface, abolishing cavities so no n Urgent surgery chemotherapy, have little effect further fluid can accumulate. Is it safe to proceed? While there on survival. is little data at present on what level of DOAC leads to no increase Curcumin in bleeding risk, knowing the level SA Pathology researchers at of drug may help with decision- Flinders Medical Centre are making regarding the risk/benefit investigating whether an active of proceeding with an invasive ingredient of turmeric, called procedure. curcumin, can be used with current therapy to treat mesothelioma. n Recurrence or extension of Research thus far suggests curcumin Curcumin is known to have anti- thrombosis while a patient is on may prove effective in inhibiting the inflammatory and anti-carcinogenic a DOAC. Unexpectedly low levels creation of new blood vessels which properties. may point to short term issues with support tumour growth. compliance. Associate Professor Sonja Klebe Firstly, researchers need to establish specialises in cancer treatment and Urgent request? that curcumin has no negative lung pathology. Her initial interest effects and prevents further fluid DOAC levels can currently be in turmeric was piqued by reports accumulation. performed urgently at both FMC and from mesothelioma patients taking the RAH. Clinicians are encouraged oral forms of curcumin. Sonja tested By piggybacking on scheduled to contact the laboratory to flag tumour cells from pleural effusions, treatment, with pleurodesis surgery the urgent nature of a sample. All finding some tumours were highly performed to ease discomfort, reported DOAC level results are responsive to curcumin. It was found researchers hope to test their accompanied by a reference range that in those patients taking curcumin hypothesis and maximise the that reflects the levels seen in patients orally, some curcumin gets into their beneficial effect of curcumin without taking these agents in clinical trials. making their patients’ lives more There is currently no prospective difficult. data linking drug levels directly to outcomes and over-interpretation After finalising preclinical data, of results should be avoided. Sonja and her team will conduct a clinical pilot study in five patients. Enquiries Sonja’s research has been supported If you have any questions about with funding from Tour de Cure, the indication for testing or the a national organisation which, since interpretation of results, please call 2007, has raised in excess of Enquiries on (08) 8222 3000 and ask $20 million and funded over 240 for the On Call Haematologist. ¥ Associate Professor Sonja Klebe individual cancer research, support (photo supplied) and prevention projects. ¥

SA Pathology Newsletter > 4 – 2016 PAGE 11 www.sapathology.sa.gov.au What is

PSA is a protein produced by the prostate gland. Men normally have low PSA levels in blood, which usually increase with age as the prostate enlarges.

The PSA test is not a specific test for by the test. For this group of men, Laboratory differences cancer; it is a marker of cancer risk. any increase represents progressive A large protein, PSA exists in many Thus a single test should not be used change and should be confirmed by different forms and each man has a as the only indicator of cancer risk. repeat tests. The PSA rate of change, different proportion of these forms If PSA level is high, a test is usually factors about the cancer and the man’s in his blood. Cancers can affect the repeated a few months later. To general health and family history proportion as well. confirm cancer presence, a prostate should all be considered. biopsy is necessary, which will also PSA is measured using an help determine how aggressive a What is ‘normal’? immunoassay, a method that uses antibodies which react with the cancer is. Because PSA increases with age, substance being measured. The result the upper limit of normal also PSA testing is used in two ways; shows how much antibody reacted increases. The mid-point of normal to identify men at risk before they with the specimen. develop cancer symptoms and to (median result) may also be used to monitor men with prostate cancer. assess risk. Because test kit manufacturers each produce their own antibody they vary PSA a risk marker What does a high PSA mean? and can react differently according to the form of PSA present. Hence Total PSA is made up of free PSA Most men with a high PSA do not a blood sample can return different (not attached to other proteins) and have prostate cancer. PSA increases results if measured in different fragments of PSA (attached to other in cancer but also in non-cancer laboratories on the same day. For proteins). If the total PSA result conditions, including benign prostatic this reason repeat tests on the same is above the midpoint for age, but hyperplasia, and any prostate man should be measured by the the proportion of free PSA is high, inflammation or infection. It can also same method where possible. this usually indicates low risk of increase after rectal examination or prostate cancer. High total PSA with ejaculation. When a laboratory switches methods, a low proportion of free PSA suggest Some prostate cancers do not release it is common practice to provide increased risk. much PSA. Patients with these types results for both the old and new tests for a period of time to allow the The rate of change in PSA level is also of cancers will produce false negative treating clinician to assess if the used as an indicator of prostate cancer results. result is truly changing. risk. If the level doubles within a year it should be followed up. At least three measurements, several months apart, Total PSA – age related reference intervals and medians are needed to confirm this. Age Reference interval Age related medium (ug/L) (ug/L) PSA monitoring < 50 years 0.2 – 3.0 0.6 For men with prostate cancer, PSA 51 – 60 years 0.2 – 4.0 0.8 is repeated over time to check cancer 61 – 70 years 0.2 – 6.5 1.1 progression. Specialists use PSA level as one factor in determining > 71 years 0.1 – 8.5 1.6 treatment. In all men PSA assay results vary day to day, hence results More information need to increase by more than Please phone Enquiries on (08) 8222 3000 and ask for the on call Biochemist. 20-30% to be significant. Resources After total prostatectomy, PSA https://www.andrologyaustralia.org/wp-content/uploads/Factsheet_PSA-Test.pdf is extremely low, at or below the http://www.prostate.org.au/ lowest level which can be measured https://labtestsonline.org/understanding/analytes/psa/tab/test ¥

SA Pathology enquiries > Metropolitan 8222 3000 > Regional and Country 1800 188 077

SA Pathology Newsletter > 4 – 2016 PAGE 12 www.sapathology.sa.gov.au