Utility of cranial MRI in non-traumatic headache patients with prior negative head CT within 1 month.

AIM: To investigate the importance of additional cranial magnetic resonance imaging (cMRI) in non-traumatic headache patients with a prior negative head computed tomography (CT) examination within 1 month. MATERIALS AND METHODS: This retrospective study analysed 162 adult patients with non-traumatic headache who underwent cMRI within 1 month of a negative initial head CT at the emergency department (ED). The diagnostic yield and false-referral rate were analysed according to the revisit duration (early [≤1 week] versus late [>1-4 weeks] revisits), patient care settings (ED versus outpatient clinics [OPC]), and clinical variables. Subsequent patient management change (PMC), such as admission and treatment (AT) or outpatient clinic treatment (OT), were also investigated. RESULTS: The overall diagnostic yield of cMRI was 17.3% (28/162) and the false-referral rate was 1.2% (2/162). The diagnostic yield of cMRI was significantly different according to the patient care settings (ED, 24.7% [21/85] versus OPC, 9.1% [7/77]; p=0.02). The diagnostic yield was highest in the ED-early-revisit group (25.4% [18/71]), 45% (9/20) in those with systemic signs, and 46.7% (14/30) in those with symptom change. Among patients with positive cMRI findings, 90% (27/30) received AT and 3.3% (1/30) received OT. Among OPC-revisit-negative cMRI patients, PMC occurred in 0% (0/50). CONCLUSION: The diagnostic yield of cMRI was relatively high for headache patients who revisited the ED earlier, especially in those with systemic signs or symptom change. Most positive cMRI cases experienced PMC. Negative cMRI in OPC-revisit patients might help clarify the benign nature of a condition.

Effects of macrophage-dependent peroxisome proliferator-activated receptor γ signalling on adhesion formation after abdominal surgery in an experimental model.

BACKGROUND: The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator-activated receptor (PPAR) γ stimulation on adhesion formation in an animal model. METHODS: Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10(-/-) ), IL-4-deficient (IL-4(-/-) ) and CD11b-Cre/PPARγ(fl) (/fl) mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR-γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression. RESULTS: Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL-4(-/-) and IL-10(-/-) mice were not affected, whereas CD11b-Cre/PPARγ(fl) (/fl) mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild-type but not CD11b-Cre/PPARγ(fl) (/fl) mice. Pioglitazone had no effect on anastomotic healing. CONCLUSION: Endogenous macrophage-specific PPAR-γ signalling affected arginase activity and macrophage polarization, and counter-regulated peritoneal adhesion manifestation. Pharmacological PPAR-γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage-dependent manner. Surgical relevance Postoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation. In an experimental model, macrophage M2 marker expression was associated with reduced peritoneal adhesion formation and involved PPAR-γ-mediated arginase activity. Macrophage-specific PPAR-γ deficiency resulted in reduced arginase activity and aggravated adhesion formation. Pioglitazone, a PPAR-γ agonist, induced M2 polarization and reduced postoperative adhesion formation without compromising anastomotic healing in mice. Pioglitazone ameliorated postoperative adhesion formation without compromising intestinal wound healing. Therefore, perioperative PPAR-γ agonism might be a promising strategy for prevention of adhesion formation after abdominal surgery.

Primary perivascular epitheloid cell tumour (PEComa) of the liver: case report and review of the literature.

PURPOSE: Perivascular epitheloid cell tumour [PEComa] is a rare neoplasm entity, characterized by perivascular epitheloid cells with a coexpression of smooth muscle and melanocytic markers. PEComas are found in a variety of localizations, though lesions within the liver are still scarcely found. Although the majority of these tumours are recognized as benign, there are some reports about advanced and aggressive tumours even with fatal outcome. By means of this case report and literary review including other 21 published cases, potential treatment modalities concerning clinical diagnostics, therapy and the follow-up care should be discussed. METHODS: The following report presents the case of a 53-year old woman with a known liver lesion, since four years under regularly sonographic controls. Finally, after a haemorrhage episode, the lesion was resected and the diagnosis found. For the literary review a systematic search for case reports published between January 1, 1999 and May 1, 2012 was performed on Pubmed. RESULTS: The only way, till now, of confirming the diagnosis is through immunohistochemical examinations. The already published Malignancy criteria by Folpe et al. must be taken carefully in question, as there are cases of malignant behaviour, that do not exactly coincide with these. CONCLUSION: Primary PEComa of the liver must be treated as potential malignant and therefore a close follow-up is demanded.

A role for Piezo2 in EPAC1-dependent mechanical allodynia.

Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1-/- mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1-Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PURPOSE: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. METHODS: Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. RESULTS: Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. CONCLUSIONS: Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-α/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL- or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.

Physiological analysis on oscillatory behavior of glucose-insulin regulation by model with delays.

In artificial pancreas, glucose level measurement and insulin infusion are often implemented in the subcutaneous tissues. Understanding the dynamics of glucose and insulin in the subcutaneous tissues is important in the regulation of blood glucose level. We propose a new two-compartmental model of glucose-insulin interaction with two explicit delays that can study the interaction of glucose in different organs and the oscillatory behavior of the glucose-insulin system. The glucose and insulin space are split into plasma compartment and interstitial fluids compartment, respectively. The four m parameters of insulin dynamics and the two delays are analyzed for their influence on the glucose-insulin regulatory system. The ranges of the six parameters are estimated for sustaining the oscillation of glucose and insulin, and ranges for different subjects are discussed based on simulation results. The effect of these parameters on the oscillatory system is related to diseases and irregular blood glucose level. The lag between glucose and insulin in the two compartments has provided an insight on the distribution and metabolism of glucose and insulin in quick- and slow-equilibrating organs and tissues. We have reported in this paper, a model that can effectively deal with concentration of glucose and insulin in the interstitial compartment. This is important for the development of artificial pancreas.

LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer.

Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, using both loss of heterozygosity analysis and customized microarray comparative genomic hybridization. LARG (leukemia-associated Rho guanine-nucleotide exchange factor) (also called ARHGEF12), identified from the analysed region, is frequently underexpressed in breast and colorectal carcinomas with a reduced expression observed in all breast cancer cell lines (n=11), in 12 of 38 (32%) primary breast cancers, 5 of 10 (50%) colorectal cell lines and in 20 of 37 (54%) primary colorectal cancers. Underexpression of the LARG transcript was significantly associated with genomic loss (P=0.00334). Hypermethylation of the LARG promoter was not detected in either breast or colorectal cancer, and treatment of four breast and four colorectal cancer cell lines with 5-aza-2'-deoxycytidine and/or trichostatin A did not result in a reactivation of LARG. Enforced expression of LARG in breast and colorectal cancer cells by stable transfection resulted in reduced cell proliferation and colony formation, as well as in a markedly slower cell migration rate in colorectal cancer cells, providing functional evidence for LARG as a candidate tumor suppressor gene.

MRSA breast abscesses in postpartum women.

BACKGROUND: Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are being increasingly observed in patients who lack traditional risk factors. While mastitis and breast abscesses are commonly encountered in post-natal women, CA-MRSA breast infections have rarely been reported. MATERIALS AND METHODS: We reviewed 15 postpartum women with methicillin-resistant Staphylococcus aureus (MRSA) breast abscesses observed in our unit from June 2005 to April 2007. Ultrasonographic examination was performed in all cases. MRSA infection was diagnosed on microbiological analysis cultured from the abscesses of these patients. RESULTS: The median age of the patients was 31.5 years. The majority of the patients were primiparae (80%). Only one patient was immunocompromised. None of the patients had history of previous breast infection and none developed recurrence. Eleven patients (73.3%) underwent aspiration of pus and four patients (26.7%) underwent incision and drainage. All the cultures were sensitive to co-trimoxazole and vancomycin. Eight (53.3%) of the cultures were also sensitive to erythromycin. CONCLUSION: CA-MRSA is an emerging problem in our obstetric population. CA-MRSA breast infections are clinically responsive to common oral antibiotics such as co-trimoxazole and erythromycin. A high index of suspicion is essential to avoid delay in the clinical response to empirical beta-lactams as these patients may benefit from an early change of antibiotics.

Gene variations in GSTM3 are a risk factor for Alzheimer's disease.

Oxidative stress is a relevant pathomechanism in Alzheimer's disease (AD) and gene variations in the glutathione S-transferase M3 gene (GSTM3), involved in the detoxification of oxygen radicals, might influence the risk of AD. We investigated the effect of three polymorphisms in GSTM3: rs1332018 (C/A); rs1799735 (del/AGG); rs7483 (G/A), on the risk of AD in 363 AD patients and 358 healthy controls. Single marker association analyses revealed that the AGG/AGG genotype of the GSTM3 rs1799735 (del/AGG) polymorphism was associated with an increased risk of AD (p=0.05), especially in the group of APOE4-allele non-carriers (p=0.004; OR=2.07). Examination of the haplotypes identified a two-marker haplotype (C/AGG) consisting of rs1332018 (C/A) and rs1799735 (del/AGG) to increase the risk of AD (p=0.029), this effect was also most prevalent in APOE4-allele non-carriers (p=0.009; OR=1.95). The population attributable risk of this haplotype in APOE4-allele non-carriers was 32.2%. Our results suggest that there is a group of AD patients in which variations in metabolism of oxidative stress play an important role.

Acoustic diagnosis of aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Phonocardiography is a promising non-invasive diagnostic tool for the assessment of aortic stenosis (AS), and time-frequency representation is a potential tool to extract information from the phonocardiogram (PCG) signal. The study aim was to develop an acoustical method to predict the severity of AS. METHODS: Normalized continuous wavelet transform (NCWT) and fast Fourier Transform (FFT) were used to perform a spectral analysis of the PCG signal. A multi-peak detection algorithm was developed to determine the dominant frequency (DF) of systolic murmurs (SM). The spectral ratio of the SM, integration of the NCWT of SM (SI), and combined information of SM and second heart sound, were also calculated. RESULTS: The DF correlated best with the hemodynamic data: r = -0.72 with aortic valve (AV) area; r = 0.63 with maximal blood velocity through the AV; and r = 0.57 with mean pressure gradient across the AV. Based on DF and SI data, the study subjects (n = 59) were classified into three categories: severe AS; moderate AS; and other cases. The acoustical and echo classifications were in agreement in 50 subjects (85%). CONCLUSION: The acoustical method developed cannot predict accurately the severity of AS, but is valuable when conducting a screening classification before an invasive method is used.

Founder mutation in the BRCA1 gene in Malay breast cancer patients from Singapore.

The mutation spectrum of the BRCA1 gene among ethnic groups from Asia has not been well studied. We investigated the frequency of mutations in the BRCA1 gene among Malay breast cancer patients from Singapore, independent of family history. By using the protein truncation test (PTT) and direct sequencing, BRCA1 mutations were detected in 6 of 49 (12.2%) unrelated patients. Four novel missense mutations in exon 11, T557A (1788A>G), T582A (1863A>G), N656S (2086A>G) and P684S (2169C>T) were identified in one patient. Two patients had missense mutations in exon 23, V1809A (5545T>C), which has been previously detected in individuals from Central and Eastern Europe. Three unrelated patients had the deleterious 2846insA frameshift mutation in exon 11. Methylation specific PCR (MSP) of the promoter region of the BRCA1 gene detected hypermethylation of tumor DNA in an additional 2 patients. Haplotype analysis using the microsatellite markers D17S855, D17S1323 and D17S1325 revealed a common haplotype for the three unrelated patients and their three relatives with the 2846insA mutation. These findings strongly suggest that the 2846insA mutation, the most common deleterious mutation in this study, may possibly be a founder mutation in breast cancer patients of Malay ethnic background.

Well-differentiated thyroid carcinoma: factors predicting recurrence and survival.

AIMS: 1) Determine the patient and tumour characteristics for well-differentiated thyroid carcinoma--towards developing a unique risk classification for our largely Chinese population. 2) Assess extent of thyroid surgery required. 3) Document prognostic value of UICC and AMES classification. METHODS: Retrospective review of 175 patients treated for primary thyroid epithelial malignancy by the Department of General Surgery at the Singapore General Hospital. RESULTS: There were 78% papillary carcinomas (PC) and 19% follicular carcinomas (FC). Female: male ratio was 3:1. Patient distribution in the UICC stages I, II, III, IV is respectively 56, 11, 31 and 2%. Twenty-six percent had hemithyroidectomy, and 74% total thyroidectomy. Neck dissections were required in 6% of FC compared to 34% of PC. Mean follow-up was 40 months. Extent of surgery did not affect PC/FC survival nor recurrence rates (p=0.53 and 0.06 respectively). Recurrences occurred in 15% FC and 9% PC. Death occurred in one FC and two PC. Survival correlated with UICC stage I/II and stage III/IV groups (p=0.04), and recurrence correlated with AMES High and Low Risk groups (p=0.004). No statistically significant difference was shown for survival between PC and FC or AMES groups and recurrence between PC and FC or UICC groups. CONCLUSIONS: Extent of thyroid surgery does not significantly affect local recurrences of PC/FC. The characterisation of thyroid carcinoma here is an important step towards developing a risk classification unique to our largely Chinese population.

Genotoxicity of human breast milk from different countries.

Dietary and/or environmental factors appear to play a key role in the international variations that exist in breast cancer incidence. The genotoxicity of breast milk extracts is being examined as a possible indicator of in vivo exposure of mammary epithelial cells to DNA-damaging agents. Breast milk samples were obtained from the UK (n = 32), a high risk country, and from Hong Kong (n = 10), India (n = 20) and Singapore (n = 20), countries of lower breast cancer incidence. The abilities of breast milk extracts to induce DNA damage detected as single-strand breaks (SSBs) in the alkaline Comet assay and to induce micronuclei in MCL-5 cells and mutations in Salmonella typhimurium YG1019 were investigated. In the Comet assay 18 of 32 (56%) UK samples induced significant increases in DNA SSBs compared with 2 of 10 (20%), 5 of 20 (25%) and 8 of 20 (40%) of the samples from Hong Kong, India and Singapore, respectively. The proportion of positive samples was significantly higher in the UK group than in the combined low breast cancer incidence group and significantly higher than in the Indian group (P < 0.05, Fisher's exact test). In the micronucleus assay 9 of 32 (28%) UK samples showed significant activity compared with 0 of 10 (0%), 2 of 20 (10%) and 3 of 20 (15%) of the samples from Hong Kong, India and Singapore, respectively. Extracts of all the aforementioned milk samples were also tested for bacterial mutagenicity. Nine of 32 (28%) UK samples induced significant activity with a dose-response effect. Although activity was detected in samples from the other countries, comparable dose-response data could not be obtained because of a lack of material. This pilot study suggests that genotoxic components occur more frequently in UK breast milk than in milk from some other countries with a lower incidence of cancer. More work is required to confirm these initial findings and to examine their relevance to variations in breast cancer incidence.

FLASH coordinates NF-kappa B activity via TRAF2.

FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.

A case of alpha-fetoprotein-producing gastric cancer.

INTRODUCTION: A case of alpha-fetoprotein (AFP)-producing gastric cancer is described in a 57-year-old Chinese woman. CLINICAL PICTURE: She presented with bleeding tendency and bone pain, and was found to have haematological evidence of disseminated intravascular coagulation and spinal metastasis. Her tumour markers, including AFP, Ca 19-9 and carcinoembryonic antigen (CEA) were elevated. In view of the elevated tumour markers, there was an exhaustive search for a primary lesion in the gastrointestinal tract, liver and ovaries. There was no radiological evidence to suggest any lesion in the chest, liver or pelvis. Lectin affinity electrophoresis of the AFP showed AFP-L2 and AFP-L3 bands, which are suggestive of a non-hepatoma malignancy. MANAGEMENT: Gastroscopy showed a gastric ulcer and she developed bleeding after the gastric biopsy which required urgent surgery. Intraoperatively she was found to have carcinomatous peritone and a malignant ulcer in the greater curve of the stomach. Histology confirmed a linitis plastica like adenocarcinoma which stains for AFP. OUTCOME: She died from multi-organ failure 3 days after surgery. CONCLUSION: AFP-producing adenocarcinoma of the stomach is not uncommon. Lectin affinity electrophoresis of AFP is helpful in the differentiation between hepatoma and non-hepatoma malignancies.

Reconstitution of caspase-8 sensitizes JB6 cells to TRAIL.

TRAIL induces apoptosis in various tumor cells. We report here that caspase-8 is required in TRAIL-induced cell death. Western blot analyses and enzyme assays showed that exposing Jurkat cells to TRAIL resulted in activation of caspases-8 followed by caspase-3 and -9. Acetyl-IETD-fluoromethylketone, a caspase-8 inhibitor, potently suppressed TRAIL-induced cell death compared to acetyl-DEVD-fluoromethylketone and acetyl-LEHD-fluoromethylketone, inhibitors of caspase-3 and caspase-9, respectively. JB6 cells, a caspase-8-deficient Jurkat variant, were completely resistant to TRAIL. However, reconstitution with a caspase-8, but not with caspase-2 or -3, sensitized JB6 cells to subsequent exposure to TRAIL. These results are indicative of the crucial function of caspase-8 in TRAIL-induced apoptosis in Jurkat cells.

Management of intraparotid facial nerve schwannomas.

BACKGROUND: The purpose of the present paper was to review the management of intraparotid facial nerve schwannoma so as to discuss its clinical presentation, evaluate the various possible diagnostic investigations, and compare the various surgical options and outcome. METHODS: Case series was undertaken of five (1.3%) patients with facial nerve schwannoma out of 400 consecutive parotidectomies at Singapore General Hospital. RESULTS: There were three men and two women with an age range of 29-65 years. Three patients presented with painless parotid lumps while two had painful parotid swellings. None had facial nerve paresis. Only one patient had preoperative diagnosis suspicious of schwannoma by fine-needle aspiration cytology (FNAC). Diagnoses were made intraoperatively. Four patients had excision with cable grafting of the nerve defect. achieving facial nerve grade II-IV (House-Brackmann scale). One patient who underwent enucleation of tumour with nerve preservation achieved grade II. CONCLUSIONS: Preoperative diagnosis is difficult but it is important for discussion of the extent and options of surgery. Fine-needle aspiration cytology holds promise in making a preoperative diagnosis. Enucleation with nerve preservation where possible seems to offer better facial function whereas nerve excision with cable graft can give satisfactory results.

Splenic angiosarcoma--an unusual cause of bleeding gastrointestinal tract.

Splenic angiosarcoma is a rare malignant vascular tumour with about 100 reported cases to date. The presentation of splenic angiosarcoma is highly variable, frequently causing diagnostic difficulty. It usually presents with splenomegaly, abdominal pain and occasionally with a microangiopathic type of anaemia. Here we report an additional case of primary angiosarcoma of the spleen presenting as a problem of bleeding from the gastrointestinal tract.

Epidemiology of Warthin's tumour of the parotid gland in an Asian population.

BACKGROUND: Recent studies have documented a number of changing demographic features in the occurrence of Warthin's tumour (adenolymphoma) of the parotid gland. In order to analyse its epidemiology in an Asian population, a retrospective study was performed on all parotid neoplasms (n = 289) operated on between 1988 and 1998. PATIENTS AND METHODS: A total of 209 consecutive patients were selected for study, 136 with pleomorphic adenomas (one bilateral) and 73 with Warthin's tumours (seven bilateral). Patients were analysed with regard to tumour incidence, age, sex and race. Smoking as an aetiological factor in the development of Warthin's tumour was also studied. RESULTS: Warthin's tumour formed 25 per cent of parotid tumours and its ratio to pleomorphic adenomas was 1 : 1.9. Multicentricity was found in 14 patients (19 per cent). The male : female ratio for Warthin's tumours was 4.6 : 1. The proportion of Warthin's tumours did not show any increasing trend relative to pleomorphic adenomas. The racial distribution of Warthin's tumours showed an increased incidence among Chinese and a reduced incidence among Malays and Indians. The adjusted odds ratio for sex and age favouring an association between smoking and Warthin's tumour was 39.5 (95 per cent confidence interval 10.5-149. 0; P < 0.0001). CONCLUSION: The incidence of Warthin's tumour is considerable among Asians although there is still male predominance. There is no rising incidence of Warthin's tumour; the trend parallels the declining smoking rate in the population. The lower incidence among ethnic groups with dark skin seems to suggest concomitant genetic factors other than environmental factors alone in histogenesis. Smokers have a 40-fold greater risk than non-smokers of developing a Warthin's tumour.