When echo gets in the way: physiological factors affecting Doppler data.

Transthoracic echocardiography (TTE) is widely used as a pre-operative screening tool. It can provide extensive information about cardiac function and underlying pathology, which could influence decisions regarding surgery. This patient was referred for TTE as part of pre-op screening, as he had a biological prosthetic aortic valve. This was a rare case where misleading TTE measurements inadvertently led to the patient being referred for transcatheter aortic valve implantation (TAVI), which delayed non-cardiac surgery.

pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

INTRODUCTION: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin's lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway. MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement. RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression. CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

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.

Imaging appearances for recurrent nasopharyngeal carcinoma and post-salvage nasopharyngectomy.

Nasopharyngeal carcinoma (NPC) is a head and neck neoplasm that occurs in endemic numbers among people of southern Chinese descent. External beam radiation to the nasopharyngeal bed and primary draining lymph node echelons is the mainstay of treatment with concurrent cisplatin-based chemotherapy for more advanced disease. Detection of residual and/or recurrent NPC has important clinical implications, as salvage protocols are available. The review aims to increase awareness of the imaging features of NPC recurrences at local and distant sites using computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET). Important changes in imaging seen in patients after nasopharyngectomy are also discussed.

Pattern of hMLH1, hMSH2 and hMSH6 expression and clinical characteristics in a sample of Malaysian colorectal carcinoma cases.

Malignant transformation from normal colonic mucosa to carcinomas may be accelerated by genetic loss or inactivation of genes of the DNA mismatch repair system. The aim of the study was to determine the local incidence and pattern of immunohistochemical expression of mismatch repair proteins namely: hMLH1, hMSH2 and hMSH6 in a series of colorectal carcinomas (CRCs) and correlate this to their clinical and pathological features. Forty-three out of 298 cases of CRCs (14.4%) showed abnormal staining pattern for mismatch repair proteins with a majority (65.1%) showing single hMLH1 loss. Tumours with mismatch repair defect (MMR-d) were frequently found at the right side of colon (p<0.001), poorly differentiated carcinomas (p<0.001), produced more mucin (p=0.007), exophytic growth (p=0.007) and were bigger (p=0.002) than tumours with no mismatch repair defect. Immunohistochemical stains for mismatch repair proteins could be done in local laboratories on these selected cases before referring for the expensive molecular test.

Assessment of tumor blood flow distribution by dynamic contrast-enhanced CT.

A distinct feature of the tumor vasculature is its tortuosity and irregular branching of vessels, which can translate to a wider dispersion and higher variability of blood flow in the tumor. To enable tumor blood flow variability to be assessed in vivo by imaging, a tracer kinetic model that accounts for flow dispersion is developed for use with dynamic contrast-enhanced (DCE) CT. The proposed model adopts a multiple-pathway approach and allows for the quantification of relative dispersion in the blood flow distribution, which reflects flow variability in the tumor vasculature. Monte Carlo simulation experiments were performed to study the possibility of reducing the number of model parameters based on the Akaike information criterion approach and to explore possible noise and tissue conditions in which the model might be applicable. The model was used for region-of-interest analysis and to generate perfusion parameter maps for three patient DCE CT cases with cerebral tumors, to illustrate clinical applicability.

Effect of processing route on the surface properties of amorphous indomethacin measured by inverse gas chromatography.

The aim of this study was to investigate the effect of processing route (i.e., quench cooling and ball milling) on the surface energy heterogeneity and surface chemistry of indomethacin (IMC). Recently developed inverse gas chromatography (IGC) methodology at finite concentrations was employed to determine the surface energy distributions of crystalline, quench cooled and milled IMC samples. Surface properties of crystalline and processed IMC were measurably different as determined by the IGC and other conventional characterization techniques: differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC was in fully amorphous form. Milled IMC showed no amorphous character by calorimetric or X-ray diffraction studies. It was demonstrated that both processed IMC samples were energetically more active than the crystalline IMC. In particular, milled IMC exhibited a relatively higher dispersive surface energy and higher surface basicity (electron donor capability). This may be attributed to the creation of surface defect sites or exposure of higher energy crystal facets during the milling process. This study confirms that processing route has notable influence on the surface energy distribution and surface acid-base character. IGC was demonstrated as a powerful technique for investigating surface properties of real-world, heterogeneous pharmaceutical materials.

Novel association of thymic carcinoid with a germline mutation in a kindred with multiple endocrine neoplasia 1 (MEN1).

Multiple endocrine neoplasia 1 (MEN1) is an autosomal dominant syndrome characterized by a triad of endocrine (parathyroid, enteropancreatic and pituitary) tumors. Familial MEN1 is defined by one first-degree relative having at least one of these 3 main tumors, and is associated with germline mutations in the MEN1 gene on 11q13 in a large proportion of cases. MEN1 patients may also develop non-endocrine tumors, notably thymic carcinoid. These are rare tumors found predominantly in men, and are a major cause of death in MEN1 due to their insidious nature, lack of effective treatment and unpredictable recurrence. Prophylactic thymectomy has been advocated for prevention but continued surveillance for recurrence is necessary. Although genotype-phenotype correlation in MEN1-related thymic carcinoid is inconsistent, there is a high prevalence of truncating mutations in this condition. We describe a father and son with MEN1, associated with thymic carcinoid (father) and the truncating mutation R29X (son), which was not previously reported in MEN1-related thymic carcinoid, and review the literature about thymic carcinoids in MEN1. Our cases illustrate the importance of a high index of suspicion for early diagnosis and lifelong surveillance in MEN1, and the utility of genetic analysis in defining surveillance for MEN1-related thymic carcinoid.

Stress cardiovascular MR in routine clinical practice: referral patterns, accuracy, tolerance, safety and incidental findings.

OBJECTIVE: The use of stress cardiovascular MR (CMR) to evaluate myocardial ischaemia has increased significantly over recent years. We aimed to assess the indications, incidental findings, tolerance, safety and accuracy of stress CMR in routine clinical practice. METHODS: We retrospectively examined all stress CMR studies performed at our tertiary referral centre over a 20-month period. Patients were scanned at 1.5 T, using a standardised protocol with routine imaging for late gadolinium enhancement. Angiograms of patients were assessed by an interventional cardiologist blinded to the CMR data. RESULTS: 654 patients were scanned (mean age 65±29 years; 63 inpatients; 9.6%). 14% of patients had incidental extracardiac findings, the commonest being liver or renal cysts (6%) and pulmonary nodules (4%). 639 patients (97.7%) received intravenous adenosine, 10 received intravenous dobutamine and 5 patients had both. Of the 15 patients who received dobutamine, 12 had no side-effects/complications, 2 experienced nausea and 1 chest tightness. Of the 644 patients who received adenosine, 43% experienced minor symptoms, 1% had transient heart block and 0.2% had severe bronchospasm requiring termination of infusion. There were no cases of hospitalisation or myocardial infarction. 241 patients also had coronary angiography. For detecting at least moderate stenosis of ≥50%, sensitivity was 86%, specificity 98% and accuracy 89%. For detecting severe stenoses of ≥70%, sensitivity was 91%, specificity 86% and overall accuracy 90%. These results compare very favourably with previous smaller research studies and meta-analyses. CONCLUSION: We conclude that stress CMR, with adenosine as the main stress agent, is well tolerated, safe and accurate in routine clinical practice.

MR imaging of tophaceous gout revisited.

Gout is the most common form of microcrystalline arthropathy, and does not usually pose a diagnostic challenge when patients have a typical presentation, appropriate biochemical picture and classical radiographic appearance. However, magnetic resonance (MR) imaging is increasingly used as the first-line imaging modality in patients with first presentation of joint pain or mass, and tophaceous gout is frequently a forgotten differential diagnosis. This article serves to review the MR imaging characteristics and appearance of gouty tophi in various joints, their clinical presentations and complications, as well as the common differential diagnoses.

Dynamic contrast-enhanced MRI of neuroendocrine hepatic metastases: A feasibility study using a dual-input two-compartment model.

Neuroendocrine hepatic metastases exhibit various contrast uptake enhancement patterns in dynamic contrast-enhanced MRI. Using a dual-input two-compartment distributed parameter model, we analyzed the dynamic contrast-enhanced MRI datasets of seven patient study cases with the aim to relate the tumor contrast uptake patterns to parameters of tumor microvasculature. Simulation studies were also performed to provide further insights into the effects of individual microcirculatory parameter on the tumor concentration-time curves. Although the tumor contrast uptake patterns can be influenced by many parameters, initial results indicate that hepatic blood flow and the ratio of fractional vascular volume to fractional interstitial volume may potentially distinguish between the patterns of neuroendocrine hepatic metastases.

Effects of a low-energy diet on sexual function and lower urinary tract symptoms in obese men.

OBJECTIVE: Abdominal obesity and type 2 diabetes mellitus are associated with erectile and urinary dysfunction in men. The extent to which sexual function and lower urinary tract symptoms (LUTSs) are improved by weight loss remains unclear. SUBJECTS: We compared the effects of 8 weeks of a low-calorie diet using meal replacements (Kicstart) on insulin sensitivity, plasma testosterone levels, erectile function (measured by the five-item version of the International Index of Erectile Function, IIEF-5), sexual desire (measured by the Sexual Desire Inventory, SDI) and LUTS (measured by the International Prostate Symptom Score, IPSS), in abdominally obese (body mass index >or=30 kg m(-2), waist circumference (WC) >or=102 cm) men (mean age 49.7 years) with uncomplicated diet or oral hypoglycemic-treated type 2 diabetes mellitus (n = 19) or without type 2 diabetes mellitus (n=25), with a control group of nondiabetic men (n = 26) with similar body mass index and WC. RESULTS: Weight loss of ∼ 10% was significantly associated with increased insulin sensitivity, plasma testosterone levels, IIEF-5 and SDI scores, as well as reduced WC and IPSS scores, in diabetic as well as nondiabetic men. The degree of weight loss was significantly associated with improvements in plasma testosterone levels (r = -0.34), erectile function (r = -0.26) and LUTS (r=0.65). Reduction in LUTS was significantly associated with increased plasma testosterone (r = -0.35), erectile function (r = -0.42) and sexual desire (r = -0.40). CONCLUSIONS: Diet-induced weight loss significantly and rapidly improves sexual function, and reduces LUTS, in obese middle-aged men with or without diabetes.

Ministry of health clinical practice guidelines: cancer screening.

The Ministry of Health publishes national clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with key recommendations from the guidelines) from the Ministry of Health clinical practice guidelines on cancer screening, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov. sg/mohcorp/publications.aspx?id=24018). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Oligodendroglial tumor chemotherapy using "decreased-dose-intensity" PCV: a Singapore experience.

The authors propose "decreased-dose-intensity" PCV (procarbazine, lomustine [CCNU], and vincristine) chemotherapy for Asian patients with oligodendroglial tumors. In this study, all seven patients with oligodendroglioma (OD) and eight with anaplastic oligodendroglioma (AO) had objective responses or stable disease. Median progression-free survival was greater than 29 months (OD) and 36.5 months or greater (AO); 86% of patients with OD and 63% with AO remain progression-free. Twenty-four Common Toxicity Criteria Grade 3/4 adverse events were noted.

Metastatic angiosarcoma to the thyroid.

BACKGROUND: Angiosarcoma (AS) in non-alpine areas is exceptionally rare, and so is metastatic AS to the thyroid. The difficulties and controversies associated with its diagnosis and management are highlighted in this case report. METHOD: Case report. RESULTS: A Chinese gentleman with AS metastatic to the thyroid presented a year after radiotherapy to his scalp AS. There was rapid expansion of the metastasis over 2 weeks and invasion of the pyriform fossa caused dysphagia and haemoptysis. The diagnosis was established by paraffin histology of the tumour post-hemithyroidectomy, after repeated fine-needle aspiration cytology was not diagnostic. Patient opted for external beam radiotherapy to the pyriform fossa instead of pharyngolaryngectomy. Residual pyriform tumour was treated with brachytherapy delivered via nasogastric tube. Unfortunately, the patient died 4 months later due to cardiac failure which was unrelated to his oncologic condition. CONCLUSION: AS metastatic to the thyroid is possible. The unexpectedly acute presentation and difficulties associated with diagnosis and management are highlighted. A useful method of delivering brachytherapy to the pyriform fossa is described.

Biopsy-proven childhood glomerulonephritis in Johor.

BACKGROUND: There has been no published study of biopsy-proven childhood glomerulonephritis in Malaysia. OBJECTIVES: To determine the pattern of childhood glomerulonephritis in Johor, Malaysia from a histopathological perspective and the various indications used for renal biopsy in children. MATERIALS AND METHODS: Retrospective study was done of all renal biopsies from children under 16 years of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The histopathological findings were reviewed to determine the pattern of biopsy-proven glomerulonephritis. The indications for biopsy, mode of therapy given after biopsy and the clinical outcome were studied. RESULTS: 122 adequate biopsies were received, 9 children had repeat biopsies. Of the 113 biopsies, minimal change disease formed the most common histopathological diagnosis (40.7%) while lupus nephritis formed the most common secondary glomerulonephritis (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed in 59.8% of the children. Of 106 patients followed-up, 84 children were found to have normal renal function in remission or on treatment. 4 patients developed chronic renal impairment and 16 reached end stage renal disease. Five of the 16 children with end stage disease had since died while 11 were on renal replacement therapy. Another 2 patients died of other complications. CONCLUSIONS: The pattern of childhood GN in our study tended to reflect the more severe renal parenchymal diseases in children and those requiring more aggressive treatment. This was because of our criteria of selection (indication) for renal biopsy. Renal biopsy where performed appropriately in selected children may not only be a useful investigative tool for histological diagnosis and prognosis but may help clinicians plan the optimal therapy for these children.

Rhinosporidiosis presenting as recurrent nasal polyps.

Rhinosporidiosis is a chronic granulomatous disease of the mucous membrane, predominantly of the nose and nasopharynx. It is uncommon in Malaysia but has been seen in immigrant workers from endemic areas like India and Sri Lanka. A case seen in Johor is reported here to highlight the need of awareness among clinicians at a time where there is increasing numbers of immigrant workers in our country. The causative organism of this disease is Rhinosporidium seeberi, which is found in stagnant waters. Sporangia and endospores of R. seeberi are seen in the granulomatous polypoidal lesions. The patients commonly present with epistaxis and nasal blockage. Complete excision is the treatment of choice for this disease. Recurrences are common despite anti-microbial treatment.

Clinics in diagnostic imaging (85). Mandible osteoradionecrosis complicated by infection.

Mandibular osteoradionecrosis is a rare but well-known complication that may be seen in patients with head and neck tumours following radiation therapy. A 42-year-old man presented with painful soft tissue swelling and a discharging sinus over the right mandible. Radiographs showed osteolytic destruction. Computed tomography confirmed bony destruction and fragmentation, as well as signs of soft tissue infection. The diagnosis of mandible osteoradionecrosis complicated by infection was confirmed by biopsy and surgically. The clinical and imaging features of osteoradionecrosis are highlighted.

Breath-hold fast recovery fast spin echo versus conventional non-breath-hold fast spin echo T2-weighted MR imaging of focal liver lesions.

INTRODUCTION: We compare the breath-hold fast recovery fast spin echo (BHFRFSE) T2-weighted and non-breath-hold fast spin echo (NBHFSE) T2-weighted sequences in image quality and lesion characterisation of focal liver lesions. MATERIALS AND METHODS: Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the 2 sequences (BHFRFSE and NBHFSE) in 79 patients with 113 liver lesions were analysed retrospectively. The image quality and nature of the lesions were evaluated by 2 experienced radiologists. RESULTS: Based on receiver operating characteristic curve analysis, lesion characterisation was comparable for both sequences. The image quality of BHFRFSE was significantly better than that of NBHFSE. The NBHFSE missed 4 malignant lesions while BHFRFSE missed 2 malignant lesions. CONCLUSION: BHFRFSE performs similarly to NBHFSE in image quality and liver lesion characterisation.

Radiologists' detection of mammographic abnormalities with and without a computer-aided detection system.

The aim of this study was to to evaluate the role of a computer-aided program (CAD) in assisting detection of mammographic lesions by radiologists not specifically trained in mammography and its potential utility in breast screening. Mammograms were evaluated by radiologists not specifically trained in mammography first without, and then with, the CAD. Finally, the mammograms were evaluated by experienced mammographers who formed the reference standard. Two hundred and ninety four breasts were studied. In 257 breasts (87.4%), the CAD system did not help with the detection of abnormalities. It assisted radiologists in detecting abnormalities in 21 breasts (7.1%) with potential for detecting abnormalities in a further 13 breasts (4.4%). Only in three cases (1%) did it cause confusion in interpretation. There is overall increased sensitivity in detecting mammographic abnormalities with the aid of the CAD system from 74.4 to 87.2%, which is statistically significant. However, it failed to detect suspicious abnormalities in 71 breasts (24.1%). The CAD system improved detection of suspicious mammographic abnormalities by radiologists who are not specifically trained in mammography. However, there is also a substantial failure to detect suspicious mammographic features that cautions against over-reliance on the system, emphasizing its role as a second reader at best.