Malaysian consensus statement on FDG PET-CT reporting format for lymphoma.

Over the past decade, 18F-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PETCT) has emerged as an important imaging modality in the management of lymphoma. Since the introduction of Deauville scoring system (2009) and the Lymphoma Response Assessment Criteria (2014), clinicians are now sharing a common language in the management of lymphoma. In Malaysia, nearly a third of PET-CT request is related to lymphoma imaging. Though there are extensive publications regarding these scoring systems and assessment criteria for lymphoma, there are hardly any literature on the reporting format for the 18F-FDG PET-CT in this disease. The variable reporting formats have on many occasions caused confusion not only to the referring clinicians but also to nuclear medicine physicians. Thus, a working committee comprising experienced nuclear medicine physicians and haematologists in Malaysia have agreed and made a joint recommendation on the standard reporting format for 18F-FDG PET-CT in Lymphoma. This recommendation will minimize inter-observer discrepancies in reporting, facilitate the understanding of the report of the referring clinicians as well as facilitate counseling between patients and clinicians in the management of the disease.

A challenging road to diagnosing transthyretin cardiac amyloidosis and using technetium-99m pyrophosphate bone scintigraphy in nuclear cardiology - A case report.

Cardiac amyloidosis (CA) is a rare form of protein deposition disease, leading to restrictive cardiomyopathy that often presents with signs and symptoms of unexplained heart failure with preserved ejection fraction (HFpEF). There are two main subtypes of CA, namely light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), which are conventionally confirmed by endomyocardial biopsy (EMB). The prognosis and treatment of the subtypes differ extensively, making it crucial to distinguish between the two. Although echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) are useful to aid in the diagnosis, they are unable to differentiate between the subtypes. Advantageously, the transthyretin cardiac amyloidosis (ATTR-CA) subtype can be diagnosed based on nuclear medicine bone scintigraphy imaging using Technetiumlabelled bone-seeking radiotracers. We report a case of a previously well, elderly gentleman who presented with acute heart failure symptoms, whereby ECHO findings were suspicious for CA. Technetium-99m pyrophosphate (99mTc- PYP) bone scintigraphy performed with complementary single photon emission computed tomography/computed tomography (SPECT/CT) at three hours post-injection revealed radiotracer uptake in the myocardium that was higher than the skeletal bone uptake. This corresponded to Perugini score of 3 along with an increased heart to contralateral lung ratio (H:CL) of 1.69. The bone scintigraphy findings together with his symptoms, ECHO, CMR, and laboratory results enabled the diagnosis of ATTR-CA to be made. In summary, bone scintigraphy offers a reliable and non-invasive method for the diagnosis of ATTR-CA. We also highlight the diagnostic pitfalls and recommendations in reporting bone scintigraphy for the indication of typing cardiac amyloidosis.

A web-based educational intervention module to improve knowledge and attitudes towards thalassaemia prevention in Malaysian young adults.

BACKGROUND: Thalassaemia is a public health burden in Malaysia and its prevention faces many challenges. In this study, we aimed to assess the effectiveness of a web-based educational module in improving knowledge and attitudes about thalassaemia prevention amongst Malaysian young adults. METHODS: We designed an interactive web-based educational module in the Malay language wherein videos were combined with text and pictorial visual cues. Malaysians aged 18-40 years old who underwent the module had their knowledge and attitudes assessed at baseline, post-intervention and at 6-month follow-up using a selfadministered validated questionnaire. RESULTS: Sixty-five participants: 47 Malays (72.3%), 15 Chinese (23.1%), three Indians (4.6%) underwent the module. Questionnaires were completed at baseline (n=65), postintervention (n=65) and at 6-month follow-up (n=60). Out of a total knowledge score of 21, significant changes were recorded across three time-points- median scores were 12 at pre-intervention, 19 at post-intervention and 16 at 6-month follow-up (p<0.001). Post-hoc testing comparing preintervention and 6-month follow-up scores showed significant retention of knowledge (p<0.001). Compared to baseline, attitudes at 6-month follow-up showed an increased acceptance for "marriage avoidance between carriers" (pre-intervention 20%, 6-month follow-up 48.3%, p<0.001) and "prenatal diagnosis" (pre-intervention 73.8%, 6-month follow-up 86.2%, p=0.008). Acceptance for selective termination however, remained low without significant change (pre-intervention 6.2%, 6-month follow-up 16.7%, p=0.109). CONCLUSION: A web-based educational module appears effective in improving knowledge and attitudes towards thalassaemia prevention and its incorporation in thalassaemia prevention programs is potentially useful in Malaysia and countries with a high internet penetration rate.

Skill validation study on sentinel lymph node biopsy in breast cancer and the challenges of false-negative, in-transit and micrometastatic nodes.

No abstract available.

A single centre study on birth of children with transfusion-dependent thalassaemia in Malaysia and reasons for ineffective prevention.

OBJECTIVE: We aimed to identify factors contributing to ineffective prevention of thalassaemia in Malaysia by studying events leading to the births of children with transfusion-dependent thalassaemia (TDT) including their parents' reproductive choices. METHODS: Thirty children with TDT born in the year 2005 to 2012 were included. Their parents underwent a semi-structured, face-to-face interview in 2012 and were followed up until 2014 to evaluate the actual decisions made during subsequent pregnancy. RESULTS: In 70% of the cases (21/30), neither parent was aware of their carrier status until their child's diagnosis. Six of the remaining nine cases did not receive accurate information or support for prenatal diagnosis and the termination option. Of the 38 parents interviewed, 20 (52.6%) indicated that they would terminate an affected pregnancy. Notably, 52.2% of Muslims supported termination. Prenatal diagnosis was made in two of the five subsequent pregnancies, with thalassaemia traits diagnosed in both fetuses. CONCLUSION: The current poor uptake of voluntary thalassaemia screening in Malaysia and inadequate access to counselling and prenatal diagnostic services contributed to ineffective prevention. A considerable number of Malaysian Muslims may accept the termination option if given access to comprehensive genetic counselling services.

Bibliography of clinical research in malaysia: methods and brief results.

This article describes the methodology of this bibliography. A search was conducted on the following: (1) bibliographic databases (PubMed, Scopus, and other databases) using search terms that maximize the retrieval of Malaysian publications; (2) Individual journal search of Malaysian healthrelated journals; (3) A targeted search of Google and Google Scholar; (4) Searching of Malaysian institutional repositories; (5) Searching of Ministry of Health and Clinical Research Centre website. The publication years were limited to 2000- 2013. The citations were imported or manually entered into bibliographic software Refworks. After removing duplicates, and correcting data entry errors, PubMed's Medical Subject Headings (MeSH terms) were added. Clinical research is coded using the definition "patient-oriented-research or research conducted with human subjects (or on material of human origin) for which the investigator directly interacts with the human subjects at some point during the study." A bibliography of citations [n=2056] that fit the criteria of clinical research in Malaysia in selected topics within five domains was generated: Cancers [589], Cardiovascular diseases [432], Infections [795], Injuries [142], and Mental Health [582]. This is done by retrieving citations with the appropriate MESH terms, as follow: For cancers (Breast Neoplasms; Colorectal Neoplasms; Uterine Cervical Neoplasms), for cardiovascular diseases (Coronary Disease; Hypertension; Stroke), for infections (Dengue; Enterovirus Infections, HIV Infections; Malaria; Nipah Virus; Tuberculosis), for injuries (Accidents, Occupational; Accidents, Traffic; Child Abuse; Occupational Injuries), for mental health (Depression; Depressive Disorder; Depressive Disorder, Major; Drug Users; Psychotic Disorders; Suicide; Suicide, Attempted; Suicidal Ideation; Substance- Related Disorders).

Decline in Cancer Diagnoses during the 'Zero COVID' Policy in Hong Kong: Indirect Spillover Impact of the COVID-19 Pandemic.

AIMS: Despite a largely successful 'zero COVID' policy in 2020, the COVID-19 pandemic disrupted routine cancer services in the city of Hong Kong. The aims of this study were to examine the trends in cancer incidence before and during the COVID-19 pandemic and estimate missed cancer diagnoses. MATERIALS AND METHODS: We used population-based data from the Hong Kong Cancer Registry 1983-2020 to examine the trends of age- and sex-standardised cancer incidence before and during the COVID-19 pandemic. We applied: (i) the annual average percentage change (AAPC) calculated using the Joinpoint regression model and (ii) the autoregressive integrated moving average (ARIMA) model to forecast cancer incidence rates in 2020. Missed cancer diagnoses in 2020 were estimated by comparing forecasted incidence rates to reported rates. A subgroup analysis was conducted by sex, age and cancer site. RESULTS: The cancer incidence in Hong Kong declined by 4.4% from 2019 to 2020 (male 8.1%; female 1.1%) compared with the long-term AAPC of 0.5% from 2005 to 2019 (95% confidence interval 0.3, 0.7). The gap between the reported and forecasted incidence for 2020 ranged from 5.1 to 5.7% (male 8.5%, 9.8%; female 2.3%, 3.5%). We estimated 1525-1596 missed cancer diagnoses (ARIMA estimate -98, 3148; AAPC 514, 1729) in 2020. Most missed diagnoses were in males (ARIMA 1361 [327, 2394]; AAPC 1401 [1353, 1460]), with an estimated 479-557 missed cases of colorectal cancer (ARIMA 112, 837; AAPC 518, 597) and 256-352 missed cases of prostate cancer (AAPC 231, 280; ARIMA 110, 594). CONCLUSION: The incidence of new cancer diagnoses declined in 2020 contrary to the long-term increase over the previous decades. Significantly lower diagnoses than expected were observed in males, particularly for colorectal and prostate cancers. Fewer reported cancer cases indicate missed diagnoses and could lead to delayed treatment that could impact future health outcomes.

Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas.

BACKGROUND: An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas. METHODS: Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m(-2) on days 1, 8, and 15 with huachansu 20 ml m(-2) daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity. RESULTS: A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679). CONCLUSION: Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.

Simulation of survivorship bias in observational studies on plasma to red blood cell ratios in massive transfusion for trauma.

BACKGROUND: Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused. METHODS: A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome. RESULTS: Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation. CONCLUSION: Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio.

CT features and quantification of the characteristics of adrenocortical carcinomas on unenhanced and contrast-enhanced studies.

AIM: To describe the morphological and contrast-agent washout characteristics of adrenocortical carcinomas (ACCs) on computed tomography (CT). MATERIALS AND METHODS: Forty-one patients with histopathologically proven ACCs were retrospectively evaluated. The morphological characteristics of the ACCs were documented and compared with surgical and histopathological findings. The percentage of contrast agent enhancement washout (PEW) and relative PEW (RPEW) were calculated for 17 patients who had the combination of unenhanced, portal venous, and 15 min delayed phase images. RESULTS: Characteristic imaging findings of ACCs included large size (38 of 41 tumours were >6 cm), well-defined margin with a thin enhancing rim (25 patients), and central stellate area of low attenuation on contrast-enhanced CT images (21 patients). Tumour extension into the inferior vena cava (IVC) with associated thrombus was identified on CT in six (14.6%) patients. Of 17 tumours evaluated, 12 (71%) had a PEW value of ≤60%, and 14 (82%) had an RPEW value of ≤40%. CONCLUSION: Large size, a well-defined margin with a thin enhancing rim, central low attenuation, and a predilection for extension into the IVC are typical morphological characteristics of ACC on CT. The contrast-washout characteristics of ACCs, in concordance with their malignant nature, share those of non-adenomas rather than adenomas.

Multimethod imaging, staging, and spectrum of manifestations of metastatic melanoma.

The incidence of melanoma has been steadily increasing. Imaging plays an important role in tumour assessment as metastatic melanoma can involve multiple organs. Computed tomography (CT) is currently the most widely used technique for tumour staging, surveillance and assessment of therapeutic response, but ultrasound, magnetic resonance imaging (MRI) and positron-emission tomography (PET)-CT also play important roles in the imaging of this tumour. In this article, we review the pathways of spread, staging according to the recently updated TNM classification, pathology, typical and atypical imaging features at common and uncommon sites, and treatment of metastatic melanoma.

Glomus Tumor of Sella Turcica With Synaptophysin Expression Mimicking Pituitary Adenoma.

Glomus tumor can rarely arise in the central nervous system as a sella turcica mass. In this article, we report a case of sellar glomus tumor in a female patient who presented at the age of 8 years with visual impairment. The tumor recurred at 4 years and 26 years after initial excision and gamma knife therapy. Histologic examination showed a monotonous population of oval cells accompanied by delicate blood vessels, features mimicking pituitary adenoma. The tumor showed histologic progression at the second recurrence. Synaptophysin staining was positive, but chromogranin and CD56 were negative. The tumor cells were negative for epithelial markers but expressed actin and SMA. Awareness of the rare occurrence of glomus tumor at this region, careful analysis of morphology, and appropriate immunohistochemical workup are essential to solve this diagnostic challenge. The clinicopathologic features of all previously reported cases are reviewed.

Phase II trial of imatinib mesylate in patients with metastatic melanoma.

Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.

Towards comprehensive population-based screening for diabetic retinopathy: operation of the North Wales diabetic retinopathy screening programme using a central patient register and various screening methods.

OBJECTIVES: To examine whether population-based retinopathy screening using a central diabetes register and employing various screening methods can achieve a high degree of population coverage to meet National Screening Committee (NSC) targets. To identify the main barriers to achieving comprehensive population coverage. To analyse referrals to ophthalmology and their outcome as a measure of previously unmet need. To assess the influence of modality of screening. SETTING: Three local health board areas in North Wales. METHODS: Establishment of a district diabetes register to hold records of all patients and subserve call-recall of general practitioner (GP) sole-care patients for screening by optometrists or digital photography. Hospital attenders were screened in diabetic clinic by direct ophthalmoscopy. Data were collected for years 1 and 2 of operation of the scheme. RESULTS: The system held a screening record for 86% of diabetic patients after year 1 and 93% after year 2. Failure to attend was the major barrier to comprehensive population screening, but this improved in year 2 (P<0.001). Both optometrists and photography identified substantial unmet need: 1% of all GP sole-care patients required immediate laser treatment. Photography was more sensitive than optometrist screening, but the additional retinopathy identified was mostly minor not requiring treatment. CONCLUSIONS: Lack of screening is much more important than modality of screening as a cause of missed sight-threatening retinopathy. A central, district-based patient register system identifies those patients not screened for further follow-up and can produce a high level of population coverage, close to NSC targets. Such schemes are needed, particularly to support primary care diabetes management.

Video assisted thoracic surgery in the management of spontaneous pneumothorax: the current status.

Over the past decade, video assisted thoracic surgery (VATS) has changed the way spontaneous pneumothorax (SP) is managed. Benefits of VATS include less postoperative pain, shorter hospital stay, and attenuated postoperative inflammatory response are evident compared with open thoracic procedures. Furthermore, the increasing acceptance by patients and referring physicians is testament to its success. Recent studies and the authors decade of experience in management of SP by VATS show that it is quick, safe, and effective, with recurrence rates generally comparable to open procedures, with some exceptions. However, selecting the correct procedure and patient, as well as knowing the limitations of the surgeons and techniques are paramount for success. Even to this day, there are considerable variations in the treatment of SP and large scale controlled studies are needed to better define timing of surgery and the role of the different procedures in the treatment and prevention of SP.

Local anaesthetic toxicity after bilateral thoracic paravertebral block in patients undergoing coronary artery bypass surgery.

We conducted a small pilot observational study of the effects of bilateral thoracic paravertebral block (BTPB) as an adjunct to perioperative analgesia in coronary artery bypass surgery patients. The initial ropivacaine dose prior to induction of general anaesthesia was 3 mg/kg, which was followed at the end of the surgery by infusion of ropivacaine 0.25% 0.1 ml/kg/hour on each side (e.g. total 35 mg/hour for a 70 kg person). The BTPB did not eliminate the need for supplemental opioids after CABG in the eight patients studied. Moreover, in spite of boluses that were within the manufacturer's recommendation for epidural and major nerve blocks, and an infusion rate that was only slightly higher than what appeared to be safe for epidural infusion, potentially toxic total plasma ropivacaine concentrations were common. We also could not exclude the possibility that the high ropivacaine concentrations were contributing to postoperative mental state changes in the postoperative period. Also, one patient developed local anaesthetic toxicity after the bilateral paravertebral dose. As a result, the study was terminated early after four days. The question of whether paravertebral block confers benefits in cardiac surgery remains unanswered. However, we believe that the bolus dosage and the injection rate we used for BTPB were both too high, and caution other clinicians against the use of these doses. Future studies on the use of BTPB in cardiac surgery patients should include reduced ropivacaine doses injected over longer periods.

Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.

PURPOSE: To study the clinical features and outcome for primary non-Hodgkin's lymphomas of the nose/nasopharynx (NNP-NHLs) according to immunophenotype. PATIENTS AND METHODS: One hundred thirteen Chinese patients with primary NNP-NHLs that belonged to the categories E, F, G, or H according to the Working Formulation (WF), with full immunophenotypic data and complete clinical follow-up data, were analyzed in this retrospective study. RESULTS: Ninety (79.6%) patients had localized (stage I or II) disease, while 23 (20.4%) had stage III or IV disease. The lymphomas in 51 (45.1%), 24 (21.3%), and 38 (33.6%) patients showed natural killer (NK)/T- (CD56-positive), T-cell, and B-cell immunophenotype, respectively. Seventy-three patients (65.8%) achieved a complete remission, of whom 34 (46.6%) subsequently relapsed. The median follow-up time for those alive was 88 months. The 5-year actuarial disease-free and overall survival rates were 34.4% and 37.9%, respectively. Multivariate analysis showed that only stage and immunophenotype were significant for survival. NK/T lymphomas were distinctive among the three immunophenotypes in the following aspects: the highest male-to-female ratio, more frequent involvement of the nasal cavity alone, higher risk of dissemination to the skin, more frequent development of hemophagocytic syndrome, and the worst prognosis (overall median survival, 12.5 months). CONCLUSION: The three immunophenotypes studied are shown to exhibit different clinical patterns. Since the NK/T phenotype carries the worst prognosis, patients who present with NNP-NHL should have their tumors analyzed for CD56 expression.