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Malaysian Journal of Medical Sciences
School of Medical Sciences, Universiti Sains Malaysia
ISSN: 1394-195X
Vol. 11, Num. 2, 2004, pp. 69-73
Untitled Document

Malaysian Journal of Medical Sciences, Vol. 11, No. 2, July 2004, pp. 69-73

ABSTRACT, 9TH NCMS, 22 - 23 MAY 2004, UNIVERSITI SAINS MALAYSIA, HEALTH CAMPUS, KUBANG KERIAN, KELANTAN - Plenary Lectures and Symposia

Code Number: mj04023

PLENARY LECTURE 1

PHOTODYNAMIC THERAPY IN THE MANAGEMENT OF CANCER

Malini Carolene Olivo

Singapore National Cancer Centre and Singapore Health Research Facilities

Optical technologies using laser spectroscopy and imaging offer the ability to non-invasively diagnose and monitor early cancers in-vivo. For many precancers and early cancers the current standard of care relies on histopathological assessment of directed biopsies in order to obtain a final diagnosis. With optical technologies, optical biopsy based diagnosis can be achieved in real time, using automated techniques, in-situ. Fluorescence imaging and spectroscopy is an emerging optical technology that offers particular promise for the diagnosis of disease, in part because of a large number of endogenous biological fluorophores. Some of the more common tissue fluorophores include the aromatic amino acids (trytophan, tyrosine and phenylalanine), the cofactor reduced nicotinamide adenine dinucleotide (NADH), flavins, porphyrins, collagen and elastin. Autofluorescence and drug induced fluorescence imaging and spectroscopy offer a means of assessing both the structural and the biochemical progression of the disease, hence, interest in its use to detect precancers has been increasing. Clinical studies at the NCC have achieved promising results in the bladder, oral cavity and cervix using exogenous porphyrin and perylene quinonoid based fluorescent markers.

It is conceivable in the near future that highly sensitive endoscopic and non-endoscopic tumour detection methods can be successfully complemented by online staging and grading, thus finally fully justifying the term ‘optical biopsy’.

In vivo confocal endomicroscopy is a non-invasive method in digital imaging of hollow organs that enables visible detection of abnormal cells on the surface and sub-surface of any hollow organ. The development of a such a method for both macroscopic and microscopic assessment was posible with a recent invention of the Optiscan fibre confocal endomicroscope by the FDA in 2002. Real time image acquisition and digistisation of optical biopsies allows for further image processing to enable derivation of menaingful real time information of the inspected site

This technique would be immensely useful in the determination of tumour margins and tumour staging during surgery. Fibre-optic fluorescence endoscopic confocal imaging technology could potentially be applied to a number of oragns systems to detect eraly disease or predisposing conditond causing premaliganat changes

Photodynamic Therapy (PDT) has been defined as the combined effect of light and a photosensitising drug to produce biological damage of therapeutic value, under conditions where either the light or the drug alone have little effect. Most PDT drugs are closely related to naturally occurring compounds and therefore have very low toxicity Whilst the concept itself is not new, developments in laser and fibreoptic technology have permitted the drug and light to be brought together within tissue in such a way as to be clinically useful. This has also been facilitated by the fact that several other ‘second generation’ compounds now in clinical trials, concentrate in certain hyperproliferative tissues relative to the surrounding healthy tissue, thus giving a favourable therapeutic ratio.

Benefits of PDT include the relative lack of trauma and pain for patients. Even where normal tissue damage does occur around the target tissue, a remarkably effective natural healing process when compared with apparently equivalent injury produced by other modalities. PDT also offers the possibility of repeat treatment, without apparent limitation. Compared to conventional chemotherapy, surgery or radiotherapy, the side-effects of PDT are minimal and largely consist of a period of skin photosensitivity, as the excess drug is excreted from the body over a period of hours to days .However, even this drawback will become unimportant as the next generation photosensitisers gain regulatory approval for widespread clinical use, since several of these exhibit much shorter optimal tissue accumulation times and excretion times. Indeed, more rapid treatment offers the possibility of PDT becoming an out-patient modality, at least for some indications.

In the past decade several thousand cancer patients have received PDT worldwide although the majority have not been part of a prospective clinical trials. It has been extremely difficult to compare results because different photosensitizers, light sources and treatment parameters have been used. Furthermore, comparison of these reports with standard cancer modalities is limited by the paucity of either long-term follow –up data or histological confirmation of complete response. The coming year will undoubtedly see a substantial expansion in the range of indications for this novel for of therapy for both oncological and non-oncological conditions.

PLENARY LECTURE II

IMAGING OF EMERGING RESPIRATORY INFECTIONS

GC Ooi

Associate Professor, Department of Diagnostic Radiology, The University of Hong Kong

The recent outbreaks of severe acute respiratory syndrome (SARS) and avian H5N1 influenza virus in East Asia has brought home the futility of frontiers and borders. East Asia has found to its cost that infectious diseases, particularly those affecting the respiratory system, do not respect boundaries. Droplet or airborne infections rapidly disseminate amongst a fluid population, assisted by rapid and seamless modern day transportation systems. As infective respiratory diseases normally culminate in an abnormal chest radiograph, imaging therefore provides one of the earliest documentation of a lower respiratory tract infection. The recent SARS outbreak has emphasized the importance of early diagnosis allowing prompt isolation of infected persons, hereby precluding spread of infection to others. Failure to effectively isolate possibly infectious person(s) resulted in the massive SARS outbreaks that occurred in Hong Kong and Beijing. Without a rapid diagnostic test, imaging is often relied upon for diagnostic purposes. This lecture will discuss the clinical utility of imaging infectious respiratory disease outbreaks such as SARS and avian H5N1 influenza, imaging modalities used, and the provision of imaging services with strict adherence to infection control and isolation measures for the containment of infection and minimization of cross infection to personnel and other patients. Main imaging modalities that can be offered as diagnostic services should include dedicated portable radiography units, digitized radiography, and computed tomography (CT) scanning service including mobile CT units.

SYMPOSIUM I

ACUTE CORONARY SYNDROME: IS THE LIGHT GETTING BRIGHTER AT THE END OF THE TUNNEL?

Rosli Md. Ali

Director of Nuclear Cardiology Unit, National Heart Institute, Kuala Lumpur, Malaysia

Acute coronary syndrome (ACS) is defined as one of two conditions: unstable angina (US) or non-ST elevation myocardial infarction (NSTEMI). The latter indicates some amount of myocardial necrosis as evidenced by a raised in serum cardiac biomarkers unlike US which dose not show a rise. The pathology behind ACS is similar to ST elevation myocardial infarction (STEMI) which occurs as a result of plaque rupture and fissure. In response to both these conditions, platelet aggregation and fibrin formation occurs. In STEMI there is a predominant of fibrin over the initial lesion and occludes the vessel lumen totally. In ACS the predominant thrombus is a white thrombus which is rich in platelet and only partially occludes the lumen.

The aim of treatment in STEMI is therefore to revascularize or open the vessel promptly to reduce the amount of myocardium that will become necrose either by thrombolytic therapy or primary angioplasty. In ACS the aim is to reduce the risk of developing into STEMI. Thus therapy is directed at preventing the sub-occlusive lesion from turning to a total occlusion.

There is a higher rate of mortality following an ACS which is almost similar as in STEMI especially within the first 2 weeks to 1 month following its occurrence. We need to quickly diagnose and aggressively treat these patients to improve their prognosis.

One of the important issues is to stratify patients with ACS into high, intermediate or low risk groups. High risk patients require more aggressive form of treatment. These can be easily differentiated from the pattern of angina in the history, ST depression in the ECG of more than 0.5 mm and the presence of a raised serum cardiac biomarkers e.g. CKMB, Troponin I or T or myoglobin.

Well proven therapies in ACS treatment are with the use of aspirin, an anti-platelet agent and heparin, an anticoagulant. Clopidogrel and Gp IIb/IIIa receptor inhibitor have been shown to be superior to routine medical therapy. Both are also beneficial when used in patients undergoing urgent percutaneous revascularization though they pose a slight but significantly higher risk of bleeding if patients are sent for bypass grafting surgery early. They need to be stopped over an appropriate duration of time before the surgery.

Low molecular weight heparin (LMWH) is superior to unfractionated heparin with a lower risk of heparin-induced thrombocytopenia and a lower incidence of myocardial infarction and death. Newer agents like fondaparinux are currently being evaluated in ACS. Fondaparinux is a synthetic pentasacharide which is a non-porcine base derivative and will be better accepted in Malaysia if proven to be as beneficial as LMWH.

There has also been a “flip-flop” in managing ACS to either conservative medical therapy or aggressively trying to revascularize these patients especially with percutaneous coronary intervention (PCI). Over the last 2-3 years the swing has been back to urgent revascularization especially with concomitant medical therapy which is able to optimize the passivation of the artery by blocking the expansion of the thrombus. The agents were listed above. The outcome following PCI is better than the existing conservative medical therapy. Benefit were seen in patients who were brought in early to the catheterization lab.

Other important aspects are as important in the treatment of ACS. Other pharmaceutical therapy are like beta-blockers and ACE-inhibitors to prevent further risk of coronary events. Statins have also been noted to stabilize the arteries and reduce subsequent risk benefits which is seen as early as 1 month following the incidence of ACS. It would appear now that lower is better with a study showing that an LDL-C of 1.6 is better than 2.5 mmol/L (what is now within the current recommended limits of <2.6 mmol/L). Other traditional risk factors for coronary heart disease need to be evaluated and intervened e.g. diabetes mellitus, a smoking history, hypertension, etc.

It is hoped that with all these measures made available today, the prognosis of an individual presenting with an ACS will be better improved.

SYMPOSIUM I

TRAFFIC LIGHTS – DIRECTING THE FLOW MEDICAL TRAFFIC

Deborah C Saltman

University of Sydney

This paper describes the application of the traffic light system of clinical-decision making and prioritisation in medical practice. Two examples will be explored – one clinical and one administrative. The first case study will focus on managing patients with multiple co-morbidities. The second case study will concentrate on appointment scheduling.

The co-morbidity case study describes the situation when more than one medical problem or symptom is present in a patient at the one time. An example would be a patient attending a consultation suffering from hypertension, diabetes, obesity and osteoarthritis. In such a consultation a doctor has to rely on the doctor’s internal traffic lights to decide what is serious and urgent (red), serious but not urgent (yellow) and stable (green).

This information can be incorporated into current medical software packages to prompt clinicians to check on the status of all co-morbidities and co-medication. In the example of our patient with the four co-morbidities mentioned, when a satisfactory blood pressure reading is recorded (green light) in the notes, a pop-up screen could remind the doctor to monitor aspects of obesity and if subsequently a non-steroidal anti-inflammatory agent is prescribed at the same time, a pop-up screen will advise about potential drug interactions (yellow light) as well as requesting traffic light settings for diet and exercise (red light).

Traffic lights are instructions delivered on roads. In health care, they can be used to assist in the effective management of services.

SYMPOSIUM II

LIGHT AND YOUR SKIN – FRIEND AND FOE

Suraiya H. Hussein

Department of Dermatology, Hospital Kuala Lumpur, Malaysia

Light of various wavelengths, occurring naturally from the sun or from artificial light sources, have a great impact on an individual’s skin. They are both beneficial and at the same time can be deleterious. On the beneficial side ultraviolet rays UVA and UVB have long been used for the treatment of such varied conditions as psoriasis, vitiligo, cutaneous T-cell lymphoma, atopic eczema, scleroderma and many others. Wavelengths in the range of visible to infra red light are used as lasers in the treatment of pigmentary, vascular and proliferative disorders on the skin, not to mention their role in hair removal and resurfacing of wrinkled and damaged skin.

On the downside, light is also a well known culprit in disorders such as cutaneous malignancies, particularly malignant melanomas, BCC and SCC. It is responsible for photoaging and all the unwanted cosmetic sequalae, which both men and women these days desperately try to undo. Furthermore, many unfortunate individuals with photosensitive disorders such as SLE, Dermatomyositis, xeroderma pigmentosa have to avoid sunlight to be able to lead a normal life.

The message is to use light sensibly so that we can reap its benefits and avoid its deleterious effects.

SYMPOSIUM II

CONTROVERSIES IN PHOTOTHERAPY FOR NEONATAL JAUNDICE

Hans Van Rostenberghe

Dept of Paediatrics, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia

Since many decades neonatal jaundice has been treated successfully with phototherapy. It was started when a nurse noticed that the jaundice of the babies who were near the window had a more rapid resolution of their jaundice than the ones more inside. Since then the mechanism of action has been elucidated as photoisomerisation of the lipid soluble unconjugated bilirubin in the skin to water soluble photo-isomers. These isomers are excreted via another pathway in the liver than the slow glucuronisation process that is the main pathway for excretion of bilirubin.

Phototherapy has been used worldwide. It has been considered as a harmless way to treat neonatal jaundice which has lead to some overuse. It has however its own side effects (e.g. retinal damage, increased bowel motility, fluid losses,) and it should at all times be considered as any other therapy with its proper indications and dosage.

A significant controversy exists around the feasibility of home phototherapy. Benefits include the ease of administration and the continued care for the child in the close to ideal home environment. Disadvantages include the lack of close medical supervision during phototherapy. Neonatal jaundice requiring phototherapy may be a sign of an underlying disease process that is evolving and that easily can be missed in the home setting. That is why many physicians feel that proper monitoring and management of the jaundiced neonate requiring phototherapy is still best done in the hospital. Furthermore in the hospital the problems of compliance (keeping the baby really under the light) may be less.

Recent studies have focused on the quality and intensity of the light given. Green, blue and white light seem to be equally effective. Light of higher intensity (double phototherapy) is more effective than a light of lower intensity (single phototherapy). Another relatively new development is the fiber-optic phototherapy. This form of therapy provides advantages in terms of ease of nursing care but is less effective than conventional phototherapy. However a combination of fiber-optic and conventional phototherapy is more effective than conventional phototherapy alone.

In conclusion, phototherapy is an effective way of treating neonatal jaundice. Newer ways of giving phototherapy seem often appealing. However, after carefully weighing advantages versus disadvantages, conventional hospital based phototherapy has still its own value.

SYMPOSIUM III

CYTOGENETICS – THE BASIS OF UNDERSTANDING CANCER

Zubaidah Zakaria

Head of Haematology Unit Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia

Cancer cytogenetics is one of the fastest growing areas in human genetics. The success in cancer cytogenetics came 35 years ago when Nowell and Hungerford (1960) detected a small karyotypic marker, the Philadelphia (Ph’) chromosome, in patients with chronic myeloid leukaemia. This acquired chromosomal abnormality, which is a perfect example of somatic mutation in a haemopoeitic stem cell disorder, was the direct cause of the neoplastic state.

The introduction of chromosome banding and high resolution techniques completely revolutionized cytogenetic analyses. Each chromosome can now be accurately identified on the basis of its unique banding pattern and chromosomes can be studied at an earlier stage and more band rich stage of mitosis where many aberrations could be characterized in greater details.

The advent of molecular cytogenetics analysis in the study of malignancy by the incorporation of a large range of techniques based around Fluorescent insitu hybridization (FISH) provides the first step in the identification of genes involved in leukaemogenesis .This is done by the identification of translocation breakpoints and commonly deleted regions using a fast and accurate method. The new multicolour karyotyping techniques MFISH combine the screening potential of cytogenetics with the accuracy of molecular genetics. These promise to unravel complex karyotypes associated with many solid tumours, and to uncover new non random rearrangements. Comparative Genomic Hybridization (CGH) has provided access to many tumour types, in identifying new regions of amplifications and deletion in a wide variety of tumour types avoiding the need for metaphase chromosomes.

Thus the clinical usefulness of various cytogenetic abnormalities as diagnostic and prognostic aids has been increasingly appreciated. It serve as a clinical tool with which important can be gained about individual patients and a central metholodology in any basic cancer research.

© Copyright 2004 - Malaysian Journal of Medical Sciences

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