Focus: Blood Cancer

JAN-MAR 17 www.singhealth.com.sg

A SingHealth Newsletter for Medical Practitioners MCI (P) 027/11/2016

FOCUS: BLOOD CANCER

Haematologic Emergencies An Overview of in the General Practice Myeloproliferative Neoplasms When to Suspect Approach to an Adult with Myeloma in Primary Care Lymphadenopathy in Primary Care

SingHealth Duke-NUS Academic Medical Centre • Singapore General Hospital • KK Women’s and Children’s Hospital • Sengkang Health • National Cancer Centre Singapore • National Dental Centre of Singapore • National Heart Centre Singapore • National Neuroscience Institute • Singapore National Eye Centre • SingHealth Polyclinics • Bright Vision Hospital Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

Haematologic Emergencies in the General Practice Adj Assoc Prof Wong Gee Chuan, Senior Consultant, Department of Haematology, Singapore General Hospital; SingHealth Duke-NUS Blood Cancer Centre

Patients with malignant haematological diseases may present with dramatic and life-threatening complications. General physicians must be able to recognise these conditions as prompt treatment can be life-saving. Hyperleukocytosis and leukostasis and febrile neutropaenia in patients with haematologic malignancies are two such conditions highlighted in this article.

mental state and unsteadiness in gait. patient presents with a high white cell HYPERLEUKOCYTOSIS AND There is also increased risk of intracra- count and symptoms suggestive of tis- LEUKOSTASIS IN HAEMATOLOGIC nial haemorrhage. sue hypoxia. MALIGNANCIES Besides affecting the central nervous Hyperleukocytosis has been variably system, eyes and lungs, other manifes- Leukostasis constitutes a medi- defined as a total white cell count tations include myocardial ischaemia, cal emergency. Prompt treatment (WBC) of 50 x 109/L or 100 x 109/L. Leu- limb ischaemia or bowel infarction. is indicated. If left untreated, the kostasis is a medical emergency charac- Leukostasis may also occur where the one-week mortality can be as high terised by hyperleukocytosis and symp- clinical picture is less typical and at a as 40%. Symptomatic patients have toms of tissue hypoperfusion. It is most WBC lower than the arbitrarily defined a worse prognosis when compared commonly seen in patients with acute figures, especially in rapidly increasing to asymptomatic patients with hy- myeloid leukaemia (AML) or chronic blasts counts. perleukocytosis alone. myeloid leukaemia (CML) in blast crisis. INVESTIGATIONS The patient should be urgently Symptoms of leukostasis occur less Besides elevated WBC and blasts in referred to the Emergency De- frequently in patients with acute lym- the FBC, evidence of tumour lysis syn- partment of a hospital, where he phoblastic leukaemia (ALL) or chronic drome (TLS) may be present in up to should be rapidly stabilised. Rap- lymphocytic leukaemia (CLL) unless the 10% of patients with leukostasis. These id cytoreduction can be achieved WBC exceeds 150 x 109/L. include raised creatinine, hyperuricae- with chemotherapy or leukapher- mia, hyperkalaemia, hyperphosphate- esis. This should be accompanied Pathologically, it is characterised by in- mia and hypocalcaemia. Disseminated by tumour lysis syndrome prophy- travascular accumulation of blasts in the intravascular coagulation (DIC) may laxis and aggressive hydration and microvasculature, resulting in increased manifest with thrombocytopaenia and allopurinol. Specialised, supportive blood viscosity and decreased perfu- an abnormal coagulation profile. care such as mechanical ventila- sion. It is also postulated that local hy- tion for respiratory failure may be poxaemia may be exacerbated by the MANAGEMENT required. high metabolic activity of the dividing The diagnosis requires a high degree of blasts and release of cytokines. suspicion. It is made clinically when a

SIGNS AND SYMPTOMS Clinically, this should be suspected when the full blood count (FBC) shows hyperleukocytosis in a patient presenting with respiratory or neurologic dis- Hyperleukocytosis in tress. Patients can present with dys- peripheral blood film pnoea and hypoxia which can be picked of a chronic myeloid leukaemia patient. up on pulse oximetry. Neurologic signs and symptoms include visual chang- This image was originally published in ASH Image es, headache, dizziness, change in Bank. Peter Maslak. Hyper- leukocytosis – CML - 1. ASH Image Bank. 2010; image number-1022. © the Ameri- can Society of Hematology.

2 Jan-Mar 2017

• Unexplained fever – neutropaenic fever with neither a clinical focus of infection nor an identified pathogen

RISK OF COMPLICATIONS The IDSA guideline considers low-risk patients as those who are expected to be neutropaenic (ANC <500 cells/ μL) for ≤7 days and those who have no active comorbidities or evidence of significant hepatic or renal dysfunction.

High-risk patients are those who are expected to be neutropaenic (ANC <500 cells/μL) for >7 days. Patients with neutropaenic fever who have ongoing comorbidities or evidence of significant hepatic or renal dysfunction are also considered to be high-risk, regardless of the neutropaenia duration.

Assessment of the risk of complications is crucial in patients with neutropaenic fever as this will dictate the approach to therapy, such as the need for inpatient admission and intravenous antibiotics.

CT scan of patient with fungal pneumonia PATHOGENESIS

This image was originally published in ASH Image Bank. Peter Maslak. Fungal pneumonia - 1. ASH Image Bank. 2007; image num- Chemotherapy-induced mucositis and ber-3475. © the American Society of Hematology. seeding of the bloodstream from endogenous flora in the gastrointestinal patients as a single oral temperature tract is believed to cause the majority FEBRILE NEUTROPAENIA IN of >38.3˚C (101˚F) or a temperature of of neutropaenic fevers. Immune defects PATIENTS WITH HAEMATOLOGIC >38.0˚C (100.4˚F) sustained for >1 hour. related to the underlying haematologic MALIGNANCIES malignancy and the immunosuppres- Neutropaenia is an absolute neutrophil sive effects of chemotherapy are other Febrile neutropaenia (FN) is one of the count (ANC) <1500 cells/μL, and severe contributory factors to the pathogen- most serious adverse events in patients neutropaenia is defined as ANC <500 esis of neutropaenic fever. with haematologic malignancies treated cells/μL or that is expected to decrease with chemotherapy. Since the magni- below 500 cells/μL during the next 48 An infectious source is identifiable in tude of the inflammatory response may hours, and profound neutropaenia is an approximately 20-30% of febrile neu- be muted in the neutropaenic patients, ANC <100 cells/μL. The risk of clinically tropaenic episodes. a fever may be the earliest and only important infections rises as the ANC sign of infection. Infections in these pa- decreases. About 80% of identified infections arise tients can progress rapidly, leading to from the patient’s endogenous flora. life-threatening complications. Initial neutropaenic fever syndromes Gram-positive bacteria (e.g. Staphy- can be classified into 3 categories: lococcus aureus, Enterococcus spp, Streptococcus pneumonia) are the FN is considered a medical emer- • Microbiologically documented in- most common causes of infections in gency. Prompt initiation of broad- fection – neutropaenic fever with the febrile neutropaenic patients. spectrum antibiotics is necessary a clinical focus of infection and an to avoid progression to sepsis associated pathogen However, infections caused by gram- and possibly death. negative bacteria (e.g. Pseudomonas • Clinically documented infection – aeruginosa, Klebsiella spp, Escherichia neutropaenic fever with a clinical coli) are associated with most serious DEFINITIONS focus (e.g. pneumonia) but with- consequences. The Infectious Diseases Society of Amer- out the isolation of an associated ica (IDSA) defines fever in neutropaenic pathogen

3 Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

Invasive fungal infections are more common in high-risk patients with prolonged fever REFERENCES syndromes, with Candida and Aspergillus Hyperleukocytosis and Leukostasis in Haematologic Malignancies spp accounting for most of these infections. 1. Porcu P, Cripe LD, Ng EW et al. Hyperleukocytic leukemias and leukostasis: a re- Viral infections, including infections caused view of pathophysiology, clinical presentation and management. Leuk Lymphoma by respiratory viruses and human herpes 2000; 39:1 viruses, are also more common in high-risk 2. Lester TJ, Johnson JW, Cuttner J. Pulmonary leukostasis as the single worst prog- patients with neutropaenia. nostic factor in patients with acute myelocytic leukemia and hyperleukocytosis. Am J Med 1985; 79:43 MANAGEMENT It is critical to recognise neutropaenic fe- 3. Azoulay E, Fieux F, Moreau D et al. Acute monocytic leukemia presenting as acute respiratory failure. Am J Respir Crit Care Med 2003; 167:1329 ver early and for empiric broad-spectrum antibiotics to be initiated promptly to 4. Porcu P, Farag S, Marcucci G et al. Leukocytoreduction for acute leukemia. Ther avoid progression to a sepsis syndrome Apher 2002; 6:1 and possible demise. Febrile Neutropaenia in Patients with Haematologic Malignancies

The managing oncologist can educate and 1. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of instruct the patient and their caregivers to antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infec- recognise symptoms that require prompt tious Diseases Society of America. Clin Infect Dis 2011; 52:e56 medical attention and to inform healthcare providers on their chemotherapy adminis- 2. Flowers CR, Seidenfeld J, Bow EJ et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy. American tration. Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2013; 31: 794

These patients should be assessed without 3. From the Immunocompromised Host Society. The design, analysis and reporting delay and referred to a hospital where em- of clinical trials on the empirical antibiotic management of the neutropenic patient. piric broad-spectrum antibiotics can be initi- Report of a consensus panel. J Infect Dis 1990; 161:397 ated immediately after blood cultures have 4. Dellinger RP, Levy MM, Carlet JM et al. Surviving Sepsis Campaign: international been obtained. International guidelines guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med advocate the administration of empiric an- 2008; 36:296 tibiotics within 60 minutes of presentation in all patients with febrile neutropaenia. Em- piric therapy aims to cover the most likely pathogens that may rapidly cause serious or life-threatening infections in neutropaenic patients.

Dr Wong Gee Chuan is a Senior Consultant in the Department of Haematology, Sin- gapore General Hospital and also Adjunct Associate Professor, Yong Loo Lin School of Medicine, National University Singapore and Adjunct Assistant Professor, Duke-NUS Medical School. Her interest is in Acute Leukaemias.

Trained in the MD Anderson Cancer Center, Houston, Texas, Dr Wong spearheaded the setup of the Leukaemia Registry and the Myeloproliferative Disorders Registry in the De- partment of Haematology, Singapore General Hospital. She also developed Leukaemia protocols, antibiotics and antifungal guidelines for immunocompromised hosts.

Besides authoring patient guidebooks on Leukaemia, Lymphoma and Febrile Neutro- paenia, she has also published extensively on Malignant Haematology and Myeloprolif- erative Disorders and conducted multiple trials in these areas. She is the Director, Acute Leukaemia Service, Department of Haematology, Singapore General Hospital. Her current research interests include treatment of acute leukaemia and management of febrile neutropaenia in immunocompromised hosts. She also has specialist accreditation in Pal- liative Medicine.

GPs can call for appointments through the GP Appointment Hotlines at 6321 4402 (SGH) or 6436 8288 (NCCS), or scan the QR code for more information.

4 Jan-Mar 2017

An Overview of Myeloproliferative Neoplasms Dr Grace Kam, Senior Consultant, Department of Haematology, Singapore General Hospital; SingHealth Duke-NUS Blood Cancer Centre

Myeloproliferative neoplasms (MPNs) are chronic haematological disorders characterised by elevated blood counts. MPNs arise from uncontrolled proliferation of haematopoietic stem cells in the bone marrow.

There are 3 main MPN subtypes: essential thrombocythaemia (ET), polycythaemia vera (PV) and myelofibrosis. ET is characterised by an elevated platelet count and PV by a high haemoglobin and haematocrit. Myelofibrosis classically demonstrates marrow fibrosis, splenomegaly, a leukoerythroblastic blood picture and varying degrees of elevated blood counts and cytopaenias. Myelofibrosis can occur as primary myelofibrosis, or can develop from the progression of ET and PV to secondary myelofibrosis.

EPIDEMIOLOGY Often the General Practitioner (GP) is ET patients may have erythromelal- Based on data from the USA and Eu- the person who first detects the elevat- gia, a condition where there is red- rope, the incidence of ET, PV and my- ed blood counts and is the initial point ness, warmth and a burning pain in the elofibrosis is 1.9-2.8 per 100,000, of contact to ensure that patients with hands and feet. PV patients classically 1.5-2.5 per 100,000 and 0.4-1.5 per elevated blood counts are appropriate- have itch, especially after a shower or 100,000 respectively. The correspond- ly referred for further evaluation. bath but in the local context, this is not ing prevalence of ET, PV and myelofi- frequent. brosis is 24-40 per 100,000, 22-30 per Symptoms in MPN are often non-spe- 100,000 and 0.5-2.7 per 100,000. cific and can be categorised into: PROGNOSIS AND COMPLICATIONS Compared to many other haematologi- Using this data, it is estimated that • Symptoms related to elevated cal malignancies, the survival in MPNs there are approximately 2,600 to 4,000 blood counts. These include giddi- is relatively good. In myelofibrosis, people in Singapore with an MPN. It ness, headache and transient visual the median survival is 7 years but can is likely that a doctor in primary care disturbances. vary from 1 to 2 years to more than 10 would encounter a patient with an MPN years. Survival in ET can measure de- either at presentation or for the treat- • Constitutional symptoms. Often cades while in PV, survival can be 20 to ment of other conditions at least once such symptoms are cytokine-relat- 30 years. Untreated however, the me- in their career. ed. The most prevalent constitu- dian survival in PV is between 6 to 18 tional symptom in MPNs is fatigue months. The median age of diagnosis is in the but may also include bone pain, fe- sixth to seventh decade of life but up to ver, night sweats, and unexplained The overriding risk in MPNs is thrombo- 20% are below the age of 40 at presen- weight loss. sis. Thrombosis is more commonly arte- tation. There is a slight male predomi- rial but can also be venous. In patients nance in PV and myelofibrosis, while • Symptoms related to hepato- with ET and extreme thrombocytosis ET is more often seen in females. The splenomegaly. Common symp- (platelet count ≥1000 x 109/L), the risk cause of MPNs is unknown. toms relate to mass effect and in- of haemorrhage is also increased. This clude early satiety, abdominal dis- is due to abnormalities in platelet func- PRESENTATION AND SYMPTOMS tension and a sensation of fullness tion and increased consumption of von Up to a quarter of patients may be asymp- or pain at the left hypochondrium. Willebrand factor. tomatic and the diagnosis made inciden- tally such as during a health screening.

5 Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

All MPNs can undergo disease transfor- In ET and myelofibrosis, the JAK2 Using the risk factors of age ≥60 years mation to acute leukaemia while ET and V617F mutation is seen in 50-60% of and a history of thrombosis, a low-risk PV can progress to secondary myelofi- patients, CALR in 15-25% and MPL in patient has zero risk factors, while a brosis. There is no current treatment 5-10%. The presence of one of these high-risk patient has one or both risk that can alter the natural history or pre- mutations demonstrates that the pa- factors. vent disease progression. tient has an MPN but a bone marrow is required to ascertain if this is ET or Low-risk ET patients with a platelet The long-term risk of progression to myelofibrosis. count <1500 x 109/L should receive acute leukaemia is approximately 5% low-dose aspirin but there is no indica- for ET, 10% for PV and 10-20% for my- Patients who do not carry any of these tion for cytoreduction. For low-risk ET elofibrosis. Rates of progression to my- mutations are referred to as ‘triple neg- patients with a platelet count >1500 elofibrosis are 5-10% for ET and 10- ative’. For triple negative patients with x 109/L or high-risk ET patients, cyto- 20% for PV. an elevated platelet or white cell count reduction is administered. Options for and do not have secondary causes to cytoreduction include hydroxyurea, DIAGNOSIS account for the elevated counts, a bone anagrelide and pegylated interferon. There are several mutations that are marrow will be required to confirm the seen in MPNs and are used in the diag- diagnosis and subtype of MPN. Some- For high-risk ET patients, hydroxyurea nostic work-up. These include: times additional investigations are re- would be the agent of choice in lower- • JAK2 V617F mutation quired to confirm the diagnosis and ex- ing the platelet count. One of the con- • Calreticulin (CALR) mutation clude reactive causes. cerns with hydroxyurea is whether it • MPL mutation could potentially contribute to the risk • JAK2 exon 12 mutation TREATMENT of acute leukaemia. From available lit- In ET and PV, the major goal of erature however, hydroxyurea has not The JAK2 V617F mutation is seen in treatment is to reduce the risk of been demonstrated to increase the risk 95% of PV patients and the JAK2 exon thrombosis. of leukaemic progression. 12 mutation in 1-3% of PV cases. If patients with elevated haemoglobin are Secondary aims of treatment are to All PV patients should receive low- negative for these two JAK2 mutations, decrease symptoms related to elevat- dose aspirin. The haematocrit should it is unlikely that the elevated haemo- ed blood counts and in patients with be maintained at less than 45%. This globin is due to polycythaemia vera extreme thrombocytosis (platelet can be achieved with regular venesec- and secondary causes of polycythaemia count >1000 x 109/L), to lessen the tion or cytoreductive therapy using ei- have to be considered. The CALR and risk of haemorrhagic events. Based ther hydroxyurea or pegylated inter- MPL mutations are not seen in PV. on the risk of thrombosis, a risk-strat- feron. Low-risk PV patients can be man- ified approach is used. aged with venesection while high-risk patients should receive cytoreduction to optimise the haematocrit.

6 Jan-Mar 2017

The management of myelofibrosis is risk/advanced myelofibrosis. The risk constitutional symptoms or symptoms often challenging. Patients may face of transplant for myelofibrosis is quite related to splenomegaly may benefit a range of concerns including throm- substantial and up to 50% may have from ruxolitinib, a JAK inhibitor. For pa- botic risk, elevated blood counts, con- transplant related complications or tients who are asymptomatic, manage- stitutional symptoms, splenomegaly, even death. ment can be expectant. anaemia, thrombocytopaenia and leukopaenia. Depending on the issues that patients have, treatment is tailored to address CONCLUSION There is no effective treatment to im- these issues. Patients with anaemia Although GPs are unlikely to be prove thrombocytopaenia and leuko- may require regular blood transfusions. directly managing the MPN, GPs paenia. Treatment has to be individu- Agents such as erythropoietin, thalido- play a vital role in ensuring that alised depending on the myelofibro- mide (with or without prednisolone) or patients with elevated blood sis-related issues, age, comorbidities, danazol can be tried but often patients counts are referred for further patient’s fitness and wishes and aims of may not have an improvement in the evaluation and working with pa- treatment. haemoglobin level, or only a transient tients’ haematologists to pro- response. vide comprehensive and holistic There is no curative treatment apart care to patients with MPNs. from allogeneic stem transplant. How- In patients with an elevated white cell ever transplant can only be considered or platelet count, cytoreduction may for fit younger patients who have high be required while patients who have

WHEN TO REFER Refer patient urgently to A&E if the patient has symptoms suggestive of hyperviscosity or a thrombotic event regardless of blood counts.

For pregnant patients with elevated blood counts who do not fulfill the criteria for urgent referral, please contact the haematologist on call for advice and early appointment.

Platelet count • Urgent referral to A&E if platelet count >1000 x 109/L OR if platelet count less than 1000 but patient has current/recent bleeding or thrombosis or neurological symptoms • Non-urgent referral if the platelet count is persistently elevated (at least 2 platelet readings above the upper limit of normal over a 4-6 week period)

Haemoglobin • Urgent referral to A&E if Hb >20 g/dL or Haematocrit ≥60% • Non-urgent referral if Hb is persistently elevated for at least 2 readings 4-6 weeks apart: women Hb >16.0 g/dL, men Hb >16.5 g/dL

White cell count • Urgent referral to A&E if blasts or a leukoerythroblastic picture is noted OR if WBC >50 x 109/L • Non-urgent referral if WBC persistently elevated (>20 x 109/L) for at least 2 readings 4-6weeks apart

Dr Grace Kam is a Senior Consultant with the Department of Haematology, Singapore General Hospital. She received her MBBS with Honours from the University of Melbourne, Australia and is a Member of the Royal College of Physicians, UK. In addition, she is also a Clinical Tutor with the Yong Loo Lin School of Medicine at the National University of Singapore.

GPs can call for appointments through the GP Appointment Hotlines at 6321 4402 (SGH) or 6436 8288 (NCCS), or scan the QR code for more information.

7 Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

When to Suspect Myeloma in Primary Care Dr Chandramouli Nagarajan, Consultant, Department of Haematology, Singapore General Hospital; SingHealth Duke-NUS Blood Cancer Centre

Multiple myeloma is a malignant Red flag symptoms for diagnosis of myeloma in patients with back pain tumour of plasma cells infiltrating the bone marrow. The median age • Age >50 years of presentation of myeloma is 65 • Pain that is worse in supine position years. A high index of suspicion is • Pain that is worse at night or awakening from sleep important for early recognition of • Pain with a band-like sensation around the body the condition, especially to avoid • Pain not responding to conventional analgesia • Associated constituitional symptoms (fever, weight loss, dehydration, recurrent infections) renal failure from setting in as es- • New or worsening neurological deficits in lower limbs tablished renal failure can change the overall prognosis in myeloma patients. Clinical manifestations of multiple myeloma Symptoms: This article gives a quick snapshot • Back pain with red flags as above or bone pain over long bones/ribs of when to suspect myeloma in pri- • Constitutional symptoms like generalised malaise, lethargy or fever mary care. • Frequent infections without reason • Peripheral neuropathy/carpal tunnel syndrome • Unexplained bleeding The SingHealth Duke-NUS • Symptoms of hypercalcaemia – Nausea, constipation, thirst Blood Cancer Centre (SDBCC) • Symptoms of hyperviscosity – Headaches, easy bruising, epistaxis, ischaemic neurologi- hosts specialty clinics for mul- cal symptoms tiple myeloma, run by Hae- Clues from investigations: matologists specially trained • Full blood count – Macrocytic anaemia, pancytopaenia, abnormal coagulation, rouleaux to manage such patients. We on blood film often have clinical trials for pa- • Liver function tests – High total protein with low albumin tients with myeloma that help • Urine – Proteinuria us to bring some of the most ef- • High ESR fective and newest discovered • Bone profile – Hypercalcaemia medicines against myeloma to • Renal profile – Renal dysfunction our patients. • Radiology – Lytic lesions in skull, vertebrae or long bones/vertebral compression frac- tures or just diffuse osteopaenia For more information on Tests to send for diagnosing myeloma (in addition to the above-mentioned): myeloma, please visit www.sgh.com.sg/myeloma. • Serum protein electrophoresis and immunofixation • Serum free light chain assay

Dr Chandramouli Nagarajan is a Consultant at the Department of Haematology, Sin- gapore General Hospital (SGH) and the SingHealth Duke-NUS Blood Cancer Centre (SDBCC). He is a Clinical Lecturer at the NUS Yong Loo Lin School of Medicine and an Adjunct Assistant Professor at the Duke-NUS Medical School. He served as a Consultant Haematologist in the Northwest of England for 2½ years before joining SGH in 2014.

His main area of interest is malignant haematology, especially lymphomas, myeloma, as well as immune and laboratory haematology. His other area of interest is clinical/medical education and he has been involved in teaching undergraduate and postgraduate students throughout his career. He has contributed as a member of several committees, was the clinical lead for blood transfusion services and has been involved in research, serving as Principal Investigator in clinical trials, during his tenure in the United Kingdom.

GPs can call for appointments through the GP Appointment Hotlines at 6321 4402 (SGH) or 6436 8288 (NCCS), or scan the QR code for more information.

8 Jan-Mar 2017

Approach to an Adult with Lymphadenopathy in Primary Care Dr Chandramouli Nagarajan, Consultant, Department of Haematology, Singapore General Hospital; SingHealth Duke-NUS Blood Cancer Centre

The lymphatic system consists of a network of lymph nodes (LN) and interconnecting lymphatic vessels. It is a slow-flow, low-pressure system serving to return filtered interstitial fluid back to the blood. They collect and process antigens from the interstitial fluid and are the sites of primary immune response.

The body has approximately 600 lymph nodes and they are located around ports of entry and along blood vessels. The peripheral lymph nodal groups are easily palpable on clinical examination, and are routinely looked for, but those in the submandibular, axillary or inguinal regions may be normally palpable in healthy individuals.

Lymphadenopathy (LAP) refers to one or more nodes that are abnormal in consistency, number or size.

The cause of LAP is usually due to an immune response to infective agents, inflammatory cells in immune disease involv- CLINICAL FACTORS TO CONSIDER FOR A PATIENT ing the lymph node or a primary or secondary neoplastic pro- WITH LAP cess, causing infiltration in the node. 1. HISTORY CONSIDERATIONS FOR LAP Since there are lots of potential causes for LAP, it is challeng- The onset, duration and progression of the LAP – Nodes ing as well as important to differentiate the benign processes that last less than 4 weeks or those that have been persistent from the malignant ones. This article summarises the broad without any size increase for a year or more are unlikely to be clinical approach to an adult presenting with LAP in primary neoplastic. This rule should not be considered absolute and care. patients who have other risk factors must be considered for further testing if in doubt. In a population-based Dutch study, about 10% of patients with unexplained LAP presenting to primary care Presence or absence of systemic symptoms – When pres- required referral to a specialist but only 1% had a malig- ent, systemic symptoms including pruritus, autoimmune-type nancy. There have been many retrospective studies sug- symptoms like rash/arthritis, etc, significant weight loss (5% gesting different percentages of risk of malignancies in over 3 months or 10% over 6 months), fever (in the absence patients presenting with unexplained LAP but the simple of infection) or drenching night sweats usually indicate an un- conclusion is that it increases with age, especially above derlying systemic cause for LAP. 40 years. The last 3 of the above are classed together as ’B‘ symptoms In primary care settings, patients 40 years of age and older in the staging system of lymphomas. Although usually asso- with unexplained LAP have about a 4% risk of cancer versus a ciated with lymphoproliferative disorders, together or sepa- 0.4% risk in patients younger than age 40. rately, they may be present in many other diseases, one of which is tuberculosis.

Since there are lots of potential causes for LAP, it is challenging as well as important to differentiate the benign processes from the malignant ones.

9 Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

Suffice to say, the presence of any of these or other systemic symptoms in most situations might indicate the need for an expeditious referral to a specialist centre for further evaluation – especially a lymph node biopsy.

Generalised vs localised LAP – Generalised LAP is defined as LAP in 2 or more non-contiguous lymph node regions and it usually indicates a systemic cause that will need evaluation. In contrast, for localised LAP the cause is likely to be in the draining area of the enlarged nodes – for example, dental/ scalp/ENT lesions could explain the cause of cervical LAP and a careful examination of these areas is warranted in patients presenting with cervical LAP.

Recent exposure to certain drugs and the onset of LAP that temporally correlates with the start of such drugs (phenyto- in, methyldopa, hydralazine, allopurinol, etc) might indicate them to be the cause, especially when associated with eo- sinophilia/skin rash.

History of sexual exposure or intravenous drug use (IVD) might serve as a clue to retroviral disease. Past history of TB, lymphoma, etc should be taken into consideration as the LAP could signify a recurrence.

2. EXAMINATION FINDINGS Site: As mentioned above, certain nodes can be felt ’normally‘ in a patient. In a thinly-built person, even a normal size lymph node could become palpable. Epitrochlear, supraclavicular or popliteal LAP should always be considered pathological and suspected for malignancy.

Size: There is no one uniform size above which a node is considered abnormal. By consensus most nodes in any site ≤1 cm are likely to be ’normal‘ and those ≥2 cm are likely to be pathological and need to be evaluated further.

An exception might be inguinal nodes which are commonly Shape: Several studies have reported that one of the most ’enlarged‘ >1 cm and may be insignificant – it has to be inter- important and sensitive (but less specific) predictive factors preted in the clinical context. Size of nodes also depends on for malignant lymph node is the Long/Short axis ratio (L/S) age (smaller sizes that might be significant for kids) and the where if that ratio is less than 2.0, malignancy is highly likely. size and build of the patient. Size does not give any clues as That is, if the width of the lymph node approaches its length, to the aetiology of the LAP. malignancy should be suspected – however note that submandibular and parotid lymph nodes can normally be round Consistency: The following can serve as a rough guide to dif- in shape. ferentiate between a benign vs malignant process. Though an ultrasound is a more objective technique for calcu- • Soft Inflammation/Infective lating this ratio, an initial clinical impression of the ratio might • Firm/Rubbery Lymphomatous process be gleaned and used for decisions on further evaluation in • Hard/Fixed Carcinomatous/Metastasis the light of the whole clinical picture. Since the sensitivity is • Fluctuant Suppurative high, L/S ratio less than 2 should be considered suspicious • Matting Infection/Malignant while a normal L/S ratio should not be taken for granted. • Pain Due to stretching of capsule/inflammation, but can also be due to rapid growth/haemorrhage or necro- Generalised LAP: Most common causes of this picture is sis within the enlarging node, hence this feature is not infectious mononucleosis syndromes, HIV infection, autoim- very useful to differentiate benign from malignant. mune diseases including Kikuchi’s disease, acute and chronic lymphoproliferative disorders like lymphomas and some leukaemias.

10 Jan-Mar 2017

Table 1 Feature Malignant Benign Factors to consider Size >2 cm <2 cm to help Consistency Hard/firm/rubbery Soft or fluctuant differentiate between Duration >2 weeks <2 weeks benign and Mobility Fixed Mobile (benign malignant nodes are mobile causes of LAP but all mobile nodes are not necessarily benign) Surroundings Attached Not attached Location Supraclavicular/ Inguinal/ Epitrochlear/ submandibular generalised (less commonly malignant)

Table 2 The acronym A ge ’ALL AGES‘ L ocation can be used to remember L ength of the time present the points to consider in A ssociated symptoms and signs differentiating benign vs G eneralised LAP malignant causes. E xtra nodal associations

S plenomegaly and fever

3. ASSOCIATED FINDINGS In particular if lymphocytosis is present, it might point towards (See Tables 1 & 2) an underlying low-grade lymphoproliferative disorder like Splenomegaly: Splenomegaly in the presence of LAP is a chronic lymphocytosis leukaemia/marginal zone lymphoma. rare occurrence in primary care (4.5% of the cases according to one study). The most likely causes for the splenomegaly It is important to note this finding, as a referral to a Haema- and LAP appearing together are infectious mononucleosis, tologist can help to confirm this diagnosis by performing a Hodgkin and non-Hodgkin lymphomas, chronic lymphocytic flow cytometry on the peripheral blood rather than subject- leukaemia and some acute leukaemias. The presence of sple- ing a patient to an unnecessary biopsy. nomegaly is relatively rare in metastatic solid cancers. Chest X-ray: Another simple investigation that can be per- Skin lesions: Autoimmune disorders, some lymphomas, cu- formed in primary care is a chest X-ray (CxR) which will help taneous cancers with secondary lymph nodes, and drug-in- to pick up mediastinal widening caused by LAP. duced LAP are potential possibilities. Serology: In the presence of corroborative history, a HIV se- 4. INVESTIGATIONS rology or an autoimmune work-up like ANA, etc might also Full blood count: A full blood count (FBC) with examination be considered while the appropriate specialist referral is be- of a peripheral blood film (PBF) is a useful and simple tool in ing initiated. If there are features suggestive of a mononu- patients with LAP. Abnormalities in the FBC including anae- cleosis syndrome (fever, sore throat, fatigue, swollen tonsils, mia, and raised white cell count with either neutrophilia or LAP, headaches), a serology for common viruses like CMV or lymphocytosis can point towards infection or immune causes. EBV (IgM anti-CMV or EBV antibody) could be performed and increasing titres documented on paired samples over 2 to 4 weeks could be suggestive of such infections.

11 Medical Appointments: 6321 4402 (SGH) Focus: Update Blood Cancer 6436 8288 (NCCS)

APPROACH TO LAP IN PRIMARY CARE

Below is a suggested pathway for managing patients with LAP, but Haemato-oncologists at the SingHealth Duke- NUS Blood Cancer Centre (SDBCC) would be happy to discuss referrals and provide guidance if you are in doubt. Patient with LAP

History (Hx) Age of patient, duration of LN, localised infection/ Physical Examination (PE) inflammation in LN draining area, pruritus/’B‘ symptoms, Site, size, shape or long to short axis ratio, localised vs exposure to TB, tobacco, animals, travel, medications, IVD generalised, consistency, tenderness, mobility or fixation, use, sexual behaviour, autoimmune symptoms, past or other associated features like splenomegaly, skin lesions family history of haematological malignancy

Consider patient’s clinical circumstances and likelihood of serious underlying illness as the possible cause of that patient’s adenopathy and symptoms based on the Hx and PE

Suspicious of Obvious mononucleosis diagnosis of self- syndrome/STDs/TB/ limited disease Unexplained or suspicious adenopathy autoimmune disorders

Upper respiratory Generalised LAP Localised LAP Consider specific infection, focal serology testing infection of skin, for EBV/CMV/HIV/ soft tissue, etc Consider performing FBC Suspicion of malignancy Quantiferon/PPD/ANA, + PBF, CxR while referral is etc while awaiting being made to the specialist specialist referral Appropriate No treatment HIV No specific diagnosis Yes Observe patient Negative for 3-4 weeks Referral to infectious Lymphocytosis disease Regression Positive Refer for specialist Persistence biopsy Referral to No further Appropriate Haematologist follow-up treatment

GPs can call for appointments through the GP Appointment Hotlines at 6321 4402 (SGH) or 6436 8288 (NCCS), or scan the QR code for more information.

12 Services Jan-Mar 2017

SingHealth Duke-NUS Blood Cancer Centre Multidisciplinary Care for Blood Cancers

There has been a steady increase in the number of patients with blood cancers like leukaemia, lymphoma and myeloma in Singapore. According to the NRDO (National Registry of Diseases Office), there has been an increase in the incidence of a type of blood cancer (in adults) called lymphomas between 1998 to 2012, with an increase of 4 cases per 100,000 population among males and 2.2 per 100,000 population among females in this time period. The SingHealth Duke-NUS Blood Cancer Centre (SDBCC) was formed to bring together special- There has been a similar increase in the incidence of ists from the Singapore General Hospital (SGH), leukaemias and an associated group of bone marrow National Cancer Centre Singapore (NCCS) and KK cancers called myeloproliferative neoplasms. Women’s and Children’s Hospital (KKH) to unify Many of these blood cancers are now curable or man- the delivery of care for patients. This ensures high- ageable by keeping them at bay with medications over quality patient-centric care that brings together long periods of time, such that they have become al- over forty specialists trained at some of the best most like chronic diseases (for example like diabetes). centres in the world. Another crucial aspect in the treatment of blood cancers is that it is on its way to becoming individualised, OUR SERVICES such that each patient’s cancer may require a carefully thought-out treatment approach based on several factors specific to that individual and their cancer. The SDBCC service line will strengthen multidisciplinary, disease-orientated care teams and patient service. This needs a good lab infrastructure and a team of lab These are the 5 key subspecialties for SDBCC: scientists to capture and integrate that information of 1. Acute Leukaemia the cancer and a dedicated team of physicians, special- u Acute Lymphoblastic Leukaemia ists, nurses and allied health professionals with experi- u Acute Myeloid Leukaemia ence to manage and navigate the patient through the treatment. 2. Myeloid Malignancies u Myelodysplastic Syndrome u Myeloproliferative Neoplasm OUR VISION & MISSION u Chronic Myeloid Leukaemia Our vision is to be an international renowned leader in 3. Lymphoid Malignancies blood cancer that delivers the best outcomes for our u Lymphoma patients. u Myeloma Our mission and strategic goals are as follows: 4. Paediatric Blood Cancers Clinical Services (at KK Women’s and Children’s Hospital) To provide a single referral channel for all blood can- 5. Cellular Therapy and Transplant cers for the delivery of unrivalled consistent, compas- (principally Haematopoietic Progenitor Cell Trans- sionate and cutting-edge clinical care. plantation or HPCT) Education u Clinical To attract and retain world-class talent while developing u Cell Processing our clinicians into world-class medical leaders through u Collection Facility lifelong continuing education in blood cancers. Research For GP referrals to the SingHealth Duke-NUS Blood To be at the forefront of translational and clinical re- Cancer Centre, please call 6321 4402 (SGH) search in order to provide innovative strategies for the or 6436 8288 (NCCS). diagnosis, stratification and treatment of our patients with blood cancers.

13 Services

OUR CLINICIANS DEDICATED TO LEADING EACH SERVICE

Acute Leukaemia Lymphoid Malignancies Myeloid Malignancies • Assoc Prof Wong Gee Chuan Lymphoma • Dr Charles Chuah Thuan Heng Senior Consultant, • Dr Diong Colin Phipps Senior Consultant, Dept of Haematology, SGH Consultant, Dept of Haematology, SGH • Assoc Prof Hwang Ying Khee, Dept of Haematology, SGH • Assoc Prof Goh Yeow Tee William • Prof Lim Soon Thye Senior Consultant, Senior Consultant/Head, Senior Consultant/Head, Dept of Haematology, SGH Dept of Haematology, SGH Division of Medical Oncology, • Dr Grace Kam Li Shan • Assoc Prof Goh Yeow Tee NCCS Senior Consultant, Senior Consultant, • Assoc Prof Goh Yeow Tee Dept of Haematology, SGH Dept of Haematology, SGH Senior Consultant, • Assoc Prof Ho Yew Leng, • Assoc Prof Ho Yew Leng, Dept of Haematology, SGH Aloysius Aloysius • Adj Assoc Prof Richard Quek Senior Consultant, Senior Consultant, Senior Consultant, Dept of Haematology, SGH Dept of Haematology, SGH Division of Medical Oncology, • Dr Yiu Cheung Richard • Dr Lao Zhentang NCCS Senior Consultant, Consultant, • Dr Tao Miriam Dept of Haematology, SGH Dept of Haematology, SGH Senior Consultant, Division of Medical Oncology, Cellular Therapy and Transplant Paediatric Blood Cancers NCCS • Assoc Prof Ho Yew Leng, (at KK Women’s and Children’s Aloysius Hospital) • Dr Lee Yuh Shan Consultant, Senior Consultant, • Assoc Prof Chan Mei Yoke Dept of Haematology, SGH Dept of Haematology, SGH Senior Consultant/Head, • Dr Chandramouli Nagarajan • Assoc Prof Hwang Ying Khee, KKH-CCF Children’s Cancer Centre Consultant, William • Prof Tan Cheng Lim, Dept of Haematology, SGH Senior Consultant/Head, Emeritus Consultant Dept of Haematology, SGH • Dr Grigoropoulos Nicholas • Assoc Prof Tan Ah Moy Francis • Assoc Prof Goh Yeow Tee Senior Consultant, Consultant, Senior Consultant, KKH-CCF Children’s Cancer Centre Dept of Haematology, SGH Dept of Haematology, SGH • Dr Joyce Lam • Dr Mohamad Farid Harunal • Dr Linn Yeh Ching Senior Consultant, Rashid Senior Consultant, KKH-CCF Children’s Cancer Centre Consultant, Dept of Haematology, SGH • Dr Soh Shui Yen Division of Medical Oncology, • Dr Tao Miriam Senior Consultant, NCCS Senior Consultant, KKH-CCF Children’s Cancer Centre • Dr Tang Pooi Ling, Tiffany Division of Medical Oncology, • Dr Rajat Bhattacharyya Consultant, NCCS Consultant, Division of Medical Oncology, • Dr Diong Colin Phipps KKH-CCF Children’s Cancer Centre NCCS Consultant, • Dr Enrica Tan Dept of Haematology, SGH Consultant, Myeloma • Dr Lee Yuh Shan KKH-CCF Children’s Cancer Centre • Dr Sathish Kumar Gopalakrishnan Consultant, • Dr Prasad Iyer Consultant, Dept of Haematology, SGH Consultant, Dept of Haematology, SGH • Dr Lim Wei Inng Francesca KKH-CCF Children’s Cancer Centre • Dr Chen Yunxin Lorraine • Dr Michaela Seng Associate Consultant, Consultant, Associate Consultant, Dept of Haematology, SGH Dept of Haematology, SGH KKH-CCF Children’s Cancer Centre • Dr Chandramouli Nagarajan • Dr Sathish Kumar Gopalakrishnan Consultant, Consultant, Dept of Haematology, SGH Dept of Haematology, SGH

For GP referrals to the SingHealth Duke-NUS Blood Cancer Centre, please call 6321 4402 (SGH) or 6436 8288 (NCCS).

14 Jan-Mar 2017

Cardiovascular Homograft Transplant (Transplant Tissue Centre)

The National Cardiovascular Homograft Bank (NCHB) was established in February 2008 by the National Heart Centre Singapore to respond to the growing request of Singaporeans in need of cryopreserved homografts. The bank supplies cryopreserved aortic, pulmonary valves and vascular tissues for patients. The main objective of NCHB is to provide cryopreserved tissues for patients and be self-sustaining through altruistic donation.

In 2012, NCHB was accredited as a Tissue Bank in accordance with the Standards of the American Association of Tissue Heart valve disease can be congenital or acquired dur- Banks (AATB). The achievement in this accreditation was ing one’s lifetime. Currently, valvular stenosis, regurgita- a result of intensive and vigorous inspections and quality tion and infective endocarditis are the most common improvements. This is to ensure that the cryopreserved heart valve diseases in Singapore. A defective or infect- cardiovascular homografts are of the highest quality and ed heart valve may be replaced with a donated heart that tissue banking activities are performed professionally, valve (human cardiovascular allograft, or homograft) or consistently and exceeding international standards. an artificial heart valve.

PAVING THE WAY FOR CARDIOVASCULAR The advantages of a cardiovascular homograft trans- HOMOGRAFTS plant include: The future of the NCHB, apart from continuing to ensure the • Anticoagulation medicine is not required highest quality of cryopreserved homografts, is to explore • Absence of haemolysis the possibility of decellularised homografts. • Higher resistance to endocarditis

Studies have shown that decellularised homografts may de- A new tissue can make a big difference in the quality of crease immunological responses, increase the durability of life for heart valve patients, and relieve them of symp- the homograft implants, and decrease the number of repeat- toms such as breathlessness, tiredness and dizzy spells. ed surgeries. It may even save them from death.

WHO CAN DONATE HOW TO SIGN UP AS A DONOR Anyone can donate. Many people assume that they are not Anyone above the age of 18 years can make this life-saving healthy enough or are too old to donate, but their heart decision by completing an Organ Donation Pledge Form valves may be working perfectly even if they have condi- and submitting it to the National Organ Transplant Unit tions such as high blood pressure or heart disease. (NOTU). This form can be obtained from the NOTU office or downloaded from the Live On website at www.liveon.sg The NCHB has an average of 10 consented donors a year since 2008. Although human heart valves are the replace- It is important for potential donors to share their wishes ment of choice for many valvular conditions, its usage has with their family, so that at the time of donation, their fam- been largely limited by availability and timeliness. Without ily will know that they are acting according to their loved a suitable human heart valve, patients may ultimately have ones’ wishes. to undergo a less ideal operation or at times, postponement in surgery. For more information, contact: National Cardiovascular Homograft Bank c/o National Heart Centre Singapore Tel: 6704 8150 Fax: 6844 9035 Email: [email protected] Website: www.nhcs.com.sg/NCHB

National Organ Transplant Unit c/o Singapore General Hospital Tel: 6321 4390

15 Services

THE JOURNEY OF A RECOVERED CARDIOVASCULAR HOMOGRAFT From the recovery to the release of homograft, the safety and standards of the homograft depend on vari- ous healthcare professionals such as the Transplant Coordinators, Medical Laboratory Technologists, Nurses, Medical Directors and Cardiothoracic Surgeons.

PROCESSING AND QUALITY SCREENING, CONSENT AND CONTROL OF CARDIOVAS- RECOVERY OF HOMOGRAFT CULAR HOMOGRAFT

SCREENING AND CONSENT OF HOMOGRAFT PREPARATION The dissection of the recovered homograft is When the Transplant Coordi- performed by the Medical Director inside a nator is notified of a death, laminar flow hood. While the dissected homo- he/she will verify on the Or- graft is soaked in a combination of antibiotics gan Donor Registry that the for 24-32 hours at a low temperature (2-8°C), potential donor is not an ob- samples of the dissected homograft are sent for jector before approaching the microbiological and histopathological testing. potential donor’s next-of-kin (NOK) to share the option of CRYOPRESERVATION tissue donation. After disinfection, each homograft is individually packed into With the NOK’s consent, the a pouch with cryopreservation solution and frozen down at a Transplant Coordinator will screen the suitability of the poten- controlled rate. The cryopreserved homograft is first stored in tial donor through his/her medical records and social history a quarantine liquid nitrogen storage tank until approved for for any risk of transmissible diseases (HIV, Hepatitis B, Hepati- clinical use by the Medical Director of the tissue bank. Cryo- tis C, syphilis, autoimmune diseases and cancer). preserved homografts have a shelf life of 5 years.

The conversation with the do- QUALITY CONTROL nor’s family will cover the de- The blood test, histopathology and dissected tissues’ micro- scription of the tissue donation biological results are reviewed by the Medical Director. The process, the benefits of dona- tests that are performed include: tion and how it can save the • Microbiology: lives of others as well as the • Aerobic bacteria reassurance that the funeral • Anaerobic bacteria arrangements will not be un- • Fungi duly delayed because of the donation. • Serology: Screening of the donor for transmissible disease • Hepatitis B • Hepatitis C RECOVERY OF THE CARDIOVASCULAR HOMOGRAFT • AIDS • Syphilis When an altruistic consent for donation has • Histology: Examination of tissue dissected been made, the respective • Myocardium healthcare professionals • Aorta involved are notified and blood is drawn from the donor. FINAL Recovery of the homograft shall take place VALIDATION within 15 hours from the time of death. The recov- The Medical Director of the tissue ered homograft is placed bank, after having obtained all neces- in media and transported sary results, will review the conformity to the National Cardiovas- to the regulations and requirements of cular Homograft Bank’s the AATB Standards before releasing laboratory. the homograft for clinical applications.

16 Appointments Jan-Mar 2017

Appointments: 6321 4402 SINGAPORE GENERAL HOSPITAL Email: [email protected] APPOINTMENTS

Dr Shum Koin Lon Dr Lee Kian Guan Dr Cassandra Associate Consultant Associate Consultant Hong Fong Yi Dept Dept Associate Consultant Internal Medicine Renal Medicine Dept Rheumatology & Immunology

Dr Indumathi Venkatachalam Dr Muli Jogi Ravi Kumar Dr Kang Hui Min Consultant Associate Consultant Associate Consultant Dept Dept Dept Infectious Diseases Diagnostic Radiology Emergency Medicine

Dr Kavitha Garuna Murthee Dr Huang Hian Liang Associate Consultant Associate Consultant Dept Dept Internal Medicine Nuclear Medicine & PET

PROMOTIONS - SENIOR CONSULTANTS

Dr Ng Shin Yi Dr Haja Mohideen Salahudeen Mohamed Senior Consultant Senior Consultant Dept Dept Anaesthesiology Diagnostic Radiology Sub-specialty Sub-specialty Intensive Care Medicine Body Imaging

Dr Emily Ho Tse Lin Dr Tan Hui Hui Senior Consultant Senior Consultant Dept Dept Endocrinology Gastroenterology & Hepatology Sub-specialty Sub-specialty Diabetes, General Hepatology, Liver Transplantation, Fatty Liver Disease, Drug-induced Endocrinology, Quality Liver Disease, Viral Hepatitis; Procedures – Diagnostic Endoscopy, Management Therapeutic Endoscopy

Dr Ng Joo Ming Dr Lee Ser Yee Matthew Senior Consultant Senior Consultant Dept Dept Hepato-pancreato-biliary & Transplant Surgery Family Medicine & Sub-specialty Continuing Care Hepatobiliary and Pancreatic Surgery, Liver Transplantation, Laparoscopic Surgery and Surgical Oncology

Dr Lam Wing Chuen Dr Tan Eng Loy Dr Sin Gwen Li Winnie Senior Consultant Senior Consultant Senior Consultant Dept Dept Dept Obstetrics & Psychiatry Nuclear Medicine & PET Gynaecology Sub-specialty Sub-specialty Old Age Psychiatry Maternal Fetal Medicine

17 Appointments

Appointments: 6321 4402 SINGAPORE GENERAL HOSPITAL Email: [email protected] PROMOTIONS - CONSULTANTS

Dr Tan Kwong Wei Dr Yeo Shen-Ann Dr Lim Chee Yeong Emile John Eugene Consultant Consultant Consultant Dept Dept Dept Diagnostic Radiology Colorectal Surgery Colorectal Surgery Sub-specialty Sub-specialty Musculoskeletal Advanced Cancer and Radiology Pelvic Floor Disease

Dr Moey Hui Lin Dr Lee Phong Ching Dr Tay Wei Yi Tammy Consultant Consultant Consultant Dept Dept Dept Endocrinology Family Medicine & Diagnostic Radiology Continuing Care Sub-specialty Breast Imaging

Dr Koay Siew Ching Dr Than Hein Dr Chung Shimin Doreen Consultant Jasmine Consultant Dept Consultant Dept Haematology Dept Gastroenterology & Sub-specialty Infectious Diseases Hepatology General Haematology, Haematology-oncology

Dr Lim Chin Hong Dr Geoffrey Sithamparapillai Samuel Consultant Consultant Dept Dept Upper Gastrointestinal & Bariatric Surgery Rehabilitation Medicine Sub-specialty Sub-specialty Gastrointestinal, Laparoscopic & General Musculoskeletal Rehabilitation Medicine Surgery, Metabolic & Bariatric Surgery

Dr Tan Yeow Leng Dr Arunachalam Sridhar Consultant Consultant Dept Dept Rehabilitation Medicine Neonatal & Developmental Medicine

PROMOTIONS - ASSOCIATE CONSULTANTS

Dr Muntasir Mannan Dr Tan Ek Khoon Dr Ngeow Jia Hao Choudhury Associate Consultant Alvin Associate Consultant Dept Associate Consultant Dept Hepato-pancreato- Dept Hand Surgery biliary & Transplant Neonatal & Surgery Developmental Medicine

18 Jan-Mar 2017

Appointments: 6294 4050 KK WOMEN’S AND CHILDREN’S HOSPITAL Email: [email protected] PROMOTIONS - SENIOR CONSULTANTS

Dr Loh Yee Jim Dr Toh Han Wei Luke Dr Arif Tyebally Senior Consultant Michael Senior Consultant Dept Senior Consultant Dept Cardiothoracic Surgery Dept Emergency Medicine Service Diagnostic & Interventional Imaging

Dr Rukshini Dr Thia Wee Hong Dr Chen Ching Kit Puvanendran Edwin Senior Consultant Senior Consultant Senior Consultant Dept Dept Dept Paediatric Family Medicine Maternal Fetal Subspecialties Service Medicine (Cardiology Service)

Dr Lee Jan Hau Dr Nandhakumar Dr Leong May Ying Senior Consultant Nagarajan Senior Consultant Dept Senior Consultant Dept Paediatric Dept Pathology & Subspecialties Paediatrics (General Laboratory Medicine (Children’s Intensive Paediatrics & Adolescent Care Unit) Medicine Service)

PROMOTIONS - CONSULTANTS

Dr Tan Yia Swam Dr Sandra Sylvia Dr Zaw Lwin Consultant Mascarenhas Consultant Dept Consultant Dept Breast Department Dept Emergency Medicine Child Development

Dr Tewani Komal Dr Amudha Jayanthi Dr Nirmal Kavalloor Girish Anand Visruthan Consultant Consultant Consultant Dept Dept Dept Gynaecological Neonatology Neonatology Oncology

Dr Odattil Geetha Dr Yip Wai Yan Dr Koh Huiting, Lynn Consultant Consultant Consultant Dept Dept Dept Neonatology Neonatology Otolaryngology

Dr Chow Chu-Tian Cristelle Dr Kang Chun-Wui Gavin Consultant Consultant Dept Dept Paediatrics (General Paediatrics & Adolescent Plastic, Reconstructive & Aesthetic Surgery Medicine Service)

19 Appointments

Appointments: 6294 4050 KK WOMEN’S AND CHILDREN’S HOSPITAL Email: [email protected] PROMOTIONS - CONSULTANTS

Dr Kong Tze Yean Dr Liu Shuling Dr Tan Tse Yeun Consultant Consultant Consultant Dept Dept Dept Plastic, Reconstructive & Reproductive Medicine Reproductive Medicine Aesthetic Surgery

PROMOTIONS - ASSOCIATE CONSULTANTS

Dr Lee Mi Li Jean Jasmin Associate Consultant Dept Family Medicine Service

NEW APPOINTMENTS

Dr Chan Yoke Hwee Dr Thia Wee Hong Assoc Prof Chang Tou Head Edwin En Kenneth Dept Head Head Children’s Intensive Dept Dept Care Unit Obstetric Ultrasound Pathology & & Prenatal Diagnostic Laboratory Medicine Unit

Appointments: 6472 2000 SENGKANG HEALTH Email: [email protected] APPOINTMENTS - SENIOR CONSULTANTS

Dr Seet Chong Meng Dr Aw Chen Wee Dr Koh Fang Yung Senior Consultant Derrick Angela Dept Senior Consultant Senior Consultant Emergency Medicine Dept Dept General Medicine General Medicine (Dermatology) (Internal Medicine)

Dr Azman Johan Dr Poon Kein Boon Senior Consultant Senior Consultant Dept Dept General Medicine Orthopaedic Surgery (Internal Medicine)

APPOINTMENTS - CONSULTANTS

Dr Tay Bee Gek Laura Dr Tan Choon Chieh Consultant Consultant Dept Dept General Medicine (Geriatric Medicine) Surgery

20 Jan-Mar 2017

Appointments: 6472 2000 SENGKANG HEALTH Email: [email protected] APPOINTMENTS - ASSOCIATE CONSULTANTS

Dr Ye Qinhao Jonathan Dr Siow Wei Ming Dr Peter Cynthia Associate Consultant Associate Consultant Assimta Dept Dept Associate Consultant General Medicine Orthopaedic Surgery Dept (Respiratory Medicine) Radiology

PROMOTION - SENIOR CONSULTANT

Dr Puneet Seth Senior Consultant Dept Emergency Medicine

PROMOTIONS - CONSULTANTS

Dr Sueziani Binte Zainudin Dr Anandakumar s/o Vellasamy Consultant Consultant Dept Dept General Medicine (Endocrinology) Orthopaedic Surgery

Dr Chew Chee Ping Dr Ho Chi Long Consultant Consultant Dept Dept Orthopaedic Surgery Radiology

Appointments: 6357 7095 NATIONAL NEUROSCIENCE INSTITUTE Email: [email protected] APPOINTMENT

Dr Ti Joanna Pearly Consultant Dept Neuroradiology

21 Appointments

Appointments: 6357 7095 NATIONAL NEUROSCIENCE INSTITUTE Email: [email protected] PROMOTIONS

Dr Daniel Oh Chia Theng Dr Tham Huilian Carol Senior Consultant Consultant Dept Dept Neurology Neurology Sub-specialty Stroke, Neuro-intensive Care

Dr Xu Zheyu Dr Purohit Bela Satish Dr Low Yin Yee Consultant Consultant Sharon Dept Dept Associate Consultant Neurology Neuroradiology Dept Neurosurgery

Appointments: 6322 9399 SINGAPORE NATIONAL EYE CENTRE Email: [email protected] APPOINTMENT

Dr Donny Hoang Q V Consultant (Part-time) Dept Surgical Retina

PROMOTIONS - CONSULTANTS

Dr Chew Chee Yen Annabel Dr Jayant Venkatramani Iyer Consultant Consultant Dept Dept Glaucoma Glaucoma

PROMOTIONS - ASSOCIATE CONSULTANTS

Dr Teo Yi Chong Kelvin Dr Ting Shu Wei Daniel Associate Consultant Associate Consultant Dept Dept General Cataract & Comprehensive General Cataract & Comprehensive Ophthalmology Ophthalmology

Dr Tsai Shih Hsiang Andrew Dr Yong Kailing Associate Consultant Associate Consultant Dept Dept General Cataract & Comprehensive General Cataract & Comprehensive Ophthalmology Ophthalmology

22 Courses Jan-Mar 2017

5th Singapore International Neurocognitive Symposium Themed Early Intervention for a Better Tomorrow, our international, regional and local experts at the 5th Singapore International Neurocognitive Symposium will be covering an extensive range of plenary sessions from clinical and bio- marker aspects of early diagnosis as well as the strategies for timely intervention. Updates on pharmacological management, non-pharmacological management and novel biomarkers in the field of dementia will be presented.

The Symposium will feature practical workshops, translational research symposium and parallel sessions. There will be a Welcome Reception, which will be a perfect opportunity for delegates to network with researchers and clinicians in the field.

Date CME Points • 16 March 2017 (Thursday) Maximum 12 points Pre-Symposium Workshop & Translational Research Symposium Contact National Neuroscience Institute • 17 – 18 March 2017 (Friday to Saturday) 11 Jalan Tan Tock Seng Main Symposium Singapore 308433 Tel: 6357 7152/7541 Venue Fax: 6256 4755 Raffles City Convention Centre Email: [email protected] 80 Bras Basah Road Singapore 189560

Registration is required. For more details or to register, visit www.nni.com.sg/education/pages/5thNeuroCog.aspx

23 Recruitment

Don’t Limit Your Challenges. www.singhealth.com.sg Challenge Your Limits.

If you are a qualified doctor/dentist, KK Women’s and Children’s GP FAST TRACK a challenging career awaits you at Hospital APPOINTMENT HOTLINES SingHealth. We seek suitably quali- Department seeking Resident fied candidates to join us as: Physicians and Staff Registrars: 6321 4402 • Women’s Anaesthesia • RESIDENT PHYSICIANS / FAMILY PHYSICIANS Departments seeking Clinical 6294 4050 Associates: • REGISTRARS / • Neurosurgical Service STAFF REGISTRARS • Neonatology 6472 2000 Interested applicants to email CV Website: www.kkh.com.sg with full personal particulars, edu- 6436 8288 Email: cational and professional qualifi- [email protected] cations (including housemanship details), career history, present and 6324 8798 expected salary, names of at least Sengkang Health two professional references, con- Departments seeking Resident tact numbers and e-mail address Physicians and Staff Registrars: 6704 2222 together with a non-returnable • Anaesthesiology photograph. • Cardiology 6357 7095 • Emergency Medicine Please email your CV to the respec- • General Surgery tive institutions’ email addresses/ • Internal Medicine 6322 9399 online career portals below with the • Neurology Reference Number MN1701. • Orthopaedic Surgery • Rehabilitation Medicine DIRECT WARD REFERRAL Website: www.singhealth.com.sg/ CONTACT NUMBERS AboutSingHealth/CorporateOverview/ sengkang-health/pages/home.aspx Email: [email protected] 6321 4822

The SingHealth Duke-NUS Aca- 6394 1180 demic Medical Centre draws on the National Heart Centre Singapore collective strengths of SingHealth Department seeking Registrars: and Duke-NUS Medical School to • Cardiothoracic Surgery drive the transformation of health- SINGHEALTH DUKE-NUS care and provide affordable, acces- Website: www.nhcs.com.sg ACADEMIC MEDICAL CENTRE sible, quality healthcare. Email: [email protected]

With 42 clinical specialties, a network of 2 Hospitals, 5 National SingHealth Polyclinics Specialty Centres, 9 Polyclinics and Seeking Resident Physicians and Bright Vision Community Hospital, Family Physicians: it delivers comprehensive, multidis- • Polyclinic (Family Medicine) ciplinary and integrated care. Website: http://polyclinic.singhealth. In 2018, the Sengkang General com.sg Hospital and Sengkang Community Email: Hospital will be completed to serve [email protected] the community in the north-east of Singapore. To enhance community care, the new Outram Community Hospital on SGH Campus will be completed in 2020. Reg. No.: 200002698Z