The t(8;21)(q22;q22) is a frequently occurring aberration in acute myeloid leukemia (AML) (18-20%) and usually correlate with French-America-British (FAB) M2 subtype. Several studies showed that patients carrying this abnormality demonstrated good response to standard chemotherapy but also have a high incidence of disease relapse. Trisomy 4 is a rare and specific chromosomal abnormality occurring in AML M2 or M4 of the FAB subtypes. We report a case of a 33-year-old female with an apparently clinical and hematologic diagnosis of acute promyelocytic leukemia (APL) in whom cytogenetic analysis revealed an abnormal karyotype with trisomy 4, in addition to t(8;21). Trisomy 4 and t(8;21) in a patient with AML is rare. The significance of t(8;21) with trisomy 4 in AML are unclear but patients bearing this abnormality are associated with a poor prognosis.
Aneusomy is an early genetic event and a characteristic feature of many solid tumors. It is often associated with poor prognosis in cancer patients. The involvement of PAX8-PPARγ rearrangement in tumorigenesis of follicular thyroid lesions has been widely assessed. However, there were few reports on aneusomy of the PPARγ gene at the 3p25 locus in follicular thyroid lesions. It remains undetermined whether these abnormalities can be translated into improved diagnosis, classification, or outcome prediction. Herein, we report three cases of follicular thyroid neoplasms [two follicular thyroid carcinomas (FTCs) and one Hurthle cell adenoma (HCA)] with 3p25 aneusomy detected by fluorescence in situ hybridization (FISH). 3p25 trisomy was observed in one FTC and one HCA while 3p25 tetrasomy was observed in one FTC. Furthermore, all three lesions did not show overexpression of PPARγ protein. Hurthle cell neoplasms (HCN) are distinct clinically and histologically from other follicular thyroid neoplasms (FTN). However, the presence of the aneusomy in HCA and FTC indicates that there could be a biological continuum between the two and chromosomal gains might play an important role in the pathogenesis of these two types of neoplasms. Despite their differences, HCN and FTN may share the same early genetic event in tumour development.
While cancer is considered to be one of the leading causes of death worldwide, there is a growing scientific and public interests on selenium as a dietary and antioxidant of many diseases, in particular, cancer. Despite advanced technology and significant improvement of surgical, chemical, hormonal and radio therapies, hepatocellular carcinoma (HCC) is still common in Asia and Africa and is increasing in the developed countries. Prognosis of HCC at an early stage is still challenging. At the moment, combination of Alpha feto protein (AFP) and ultrasonography tests offers more accurate and sensitive results for the diagnosis of HCC. Selenium (also known as the moon element) has been recognized for almost 49 years as an antioxidant and anti cancer agent. The weight of evidence supports the position of selenium as an anti cancer agent for HCC but the molecular mechanism of how selenium inhibits HCC is still unknown. Numerous theories have been proposed and selenium induced apoptosis and cell cycle arrest is the predominant one so far.
Functional recovery in the immediate post stroke period predicts the long-term prognosis of post stroke patients. Despite the advancement in stroke rehabilitation in improving the physical function of survivors, there are other factors that may influence functional recovery. We aimed to assess the functional recovery of ischaemic stroke patients attending a tertiary hospital and its associated factors in order to make recommendations for post stroke care after hospital admission. A three months prospective observational study looking at functional recovery using the Modified Barthel’s Index (MBI) and depression (Patient Heath Questionnaire-9) score of post stroke patients. There were 46 ischaemic stroke patients who were recruited for the study. At three months, only 37 patients were eligible for analysis. The mean age was 67.2 (SD 11) years with the Malays (50%) making up the majority of the patients, followed by Chinese (41.3%) and Indians (8.7%). There was a total of seven (15.2%) deaths. Hypertension was the most common risk factor (89.1%) followed by dyslipidaemia (65.2%) and diabetes mellitus (63.0%). The mean MBI difference was 45.2 (SD 27.0) with a median MBI of 17.0(IQR 33.0) at baseline compared to 85.0(IQR 42.0) at three months (p < 0.001, CI 35.98,55.45). The prevalence of depression (PHQ-9≥10) was 21.6%. Lower functional recovery was found among depressed patients (p
Bcl-2 is an anti-apoptotic protein belonging to a family of proteins that act as regulators of apoptosis in mammalian cells. Bcl-2 expression has previously been reported in normal breast ductal cells and its involvement in the hormonal regulation of hyperplasia and involution was further suggested, and it was thought to be expressed through hormonedependent pathways. Bcl-2 is a cytoplasmic oncoprotein which is highly expressed in human solid tumours. In breast cancer cells, however, Bcl-2 expression is down regulated, the exact mechanism and the effects of which are not clearly defined, as bcl-2 expression appears to be inversely correlated with the presence of p53 mutations. This work aimed at investigating the expression of bcl-2 in invasive ductal carcinoma of the breast utilizing an immunohistochemistry assay as well as studying the clinical correlations of bcl-2. Bcl-2 was detected in 43.7% of 382 invasive ductal carcinoma study cases. Its expression correlated positively, with lower age of patients, higher histological grades, large tumour sizes, estrogen receptor positivity and progesterone receptor negativity. However, the statistical correlations were weak. With the data obtained, it was found that the expression of bcl-2 correlated with unfavourable prognoses. Furthermore, bcl-2 detection alone may not be very helpful in consolidating a clinical diagnosis.
Despite being the major cause of cancer-related death in Malaysian women,local data on patterns of breast cancer relapse and their long term outcomes are still scarce. We conducted a retrospective study on all patients treated for non-metastatic invasive breast cancer in 1999-2000 at the University of Malaya Medical Centre (UMMC), who subsequently developed relapse. We sought to analyse the patterns of relapse, their associated clinicopathological features and the overall survival ratefollowing the relapses. Univariate and multivariate analyses were used to analyse demographics and clinicopathological factors. Survival was analysed using the Kaplan and Meier method and compared by the log rank test. A total of 268 patients with a mean age of 50, were identified for the study. At a median follow-up of 50 months, 73 patients (27.2%) had relapsed. Local, regional and distant relapse rates were 5.5%, 1.9% and 19.8% respectively, whereas, the 5-year survival rates were 61%, 40% and 21% respectively (p < 0.01). Most relapses occurred within the first five years of diagnosis. Patients with long disease-free interval had better survival. The most common distant relapse site was the lungs while bone was the distant relapse site with the best prognosis. Disease stage, nodal status and oestrogen receptor status were found to have correlation with the risk of relapse. We concluded that the survival of patients with relapsed breast cancer was associated with the site(s) of first relapse and the disease free interval and clinicopathological factors can be used to predict the risk of relapse.
Chondrosarcoma is the third most common primary tumour of the bone, after myeloma and osteosarcoma. Most of the chondrosarcoma grow slowly and rarely metastasize, and they have an excellent prognosis after adequate surgery. However most of them are chemo or radio-resistant. We report a case of primary chondrosarcoma of proximal humerus in a 36-year-old female who presented with a six years history of left shoulder swelling and restricted range of motion. Trucut biopsy showed a well-differentiated chondrosarcoma. The patient underwent forequarter amputation of left upper limb and was started on chemotherapy following operation.
Cataract is the most common cause of blindness in the world. An attack of phacolytic and phacomorphic glaucoma as a result of neglected cataract constitutes a medical emergency that must be addressed immediately. Ocular emergencies such as these is challenging for the surgeon with guarded or poor prognosis. We describe the presentation, management and prognosis of three cases of phacomorphic and phacolytic glaucoma. All three patients underwent aggressive management of intraocular pressure. Despite successful cataract operation with implantation of intraocular lens, there was only mild improvement of the vision. Optic nerve and pupil functions were permanently affected following the insult. Phacomorphic and phacolytic glaucoma present a very challenging problem to the surgeon with poor visual outcome. Public health education and awareness are important and health workers should encourage patients with cataract to seek early treatment for better prognosis.
This was a case of a young lady presenting with 10 year history of a mass in the right eye. It was found to be an adenocarcinoma of the lacrimal gland from histopathological biopsy. She underwent wide excision, orbital exenteration and reconstruction with a free rectus abdominis flap. Unfortunately, she had a tumour recurrence which was not controlled by radiotherapy and a second excision. The behavior of the tumour was aggressive, resulting in widespread metastases. She passed away within a year of her presentation. Of note, the histopathology report from the second excision turned out to be sarcomatoid carcinoma. This is described in the literature as dedifferentiation, or high grade transformation (HGT). Occurrence of dedifferentiation in salivary gland tumours is well-established, but not as well-described in lacrimal gland tumours. In this case, there was a severely delayed presentation of a lacrimal gland adenocarcinoma in a young person, which underwent dedifferentiation into a sarcomatoid carcinoma. This phenomena is associated with aggressive tumour biology behavior and poor prognosis, despite surgery and radiotherapy.
Infection by hepatitis B virus (HBV) is a major global health-care problem. HBV is an accepted factor in the elevated risks for liver disease such as cirrhosis and development of hepatocellular carcinoma. This problem is particularly prevalent in the Asia-Pacific region which includes Malaysia. During infection, the hepatitis B e antigen (HBeAg) is produced in the hosts. This antigen is an important serological marker for diagnosing chronic hepatitis B. Seroconversion to anti-body (anti-HBe) corresponds to the improvement of disease prognosis. However, certain mutations such as the core promoter dual mutations (A1762G1764→T1762A1764), the codon 15 variants (C1858/ T1858) and the precore stop codon mutations (TGG→TAG) can affect the HBeAg expression. This has diagnostic and clinical implications. Besides that, the HBV can be grouped into eight genotypes (A to H). Moreover, genotypic subtypes and recombinants have been observed as well. Studies have observed that these can differ in their affiliations with the mutations above as well as with disease prognosis.
Introduction: There are many factors that determine the survival of patients with VSD. Among these include size of VSD, position, pulmonary hypertension, bacterial sepsis, valvular involvement, associated anomalies with VSD, associated syndromes and age at first diagnosis. There has been no published local data as far as we know and this information will be useful especially for consultation with parents. Even though VSD in general has a good prognosis, whenever they have added risks for example pulmonary hypertension then they are at risk of further morbidity and mortality. Objective: To determine the factors that are associated with survival of patients with VSD. Design: Retrospective cohort. Materials and methods: All cases of isolated VSDs admitted to HUSM from 1996 to 2003 were reviewed. Results: Univariate Cox regression of survival time of patients with VSDs revealed that 4 factors had prognostic significance namely bacterial sepsis (HR= 287.7, 95% CI 51.1, 1618.5, P < 0.001), Down syndrome (HR = 14.89, 95% CI 3.00, 73.92, P = 0.001), pulmonary hypertension (HR=14.58, 95% CI 1.69, 125.7, P=0.015) and large VSDs (HR=8.23, 95% CI 1.5, 45, P=0.015). Bacterial sepsis was the only significant prognostic factors for the survival of patients with VSDs using the multivariate Cox proportional hazard model. Conclusion: Bacterial sepsis, pulmonary hypertension, large VSD and Down syndrome were the significant prognostic factors from Univariate Cox analysis, however bacterial sepsis was the only significant prognostic factor from Multivariate Cox analysis.
Metastatic spread of tumors to the skull is quite unusual and often represents diagnostic and therapeutic issues. Skull involvement can be observed in various neoplasms of epithelial origin and are most often due to lung, breast, thyroid, kidney and prostate cancers. However, skull metastases from hepatocellular carcinoma (HCC) have been rarely reported. The prognosis for patients with hepatocellular carcinoma is so poor that treatment of such distant metastatic lesion cannot be achieved before death occurs due to the primary malignancy. Therefore, the clinical manifestations of cranial metastasis prior to that of primary hepatocellular carcinoma have rarely been reported. This case illustrates a rare case of skull metastasis as an initial manifestation of hepatocellular carcinoma. Although a solitary skull metastasis prior to the diagnosis of HCC demonstrates rare metastatic behavior for HCC, especially in Asia, skull metastases from HCC should be included in the differential diagnosis of skull tumors, even if the patient is asymptomatic of liver cirrhosis.
Metabonomics can be used to quantitatively measure dynamic biochemical responses of living organisms to physiological or pathological stimuli. A range of analytical tools such as high-resolution nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) combined with multivariate statistical analysis can be employed to create comprehensive metabolic signatures of biological samples including urine, plasma, faecal water and tissue extracts. These metabolic signatures can reflect the physiological or pathological condition of the organism and indicate imbalances in the homeostatic regulation of tissues and extracellular fluids. This technology has been employed in a diverse range of application areas including investigation of disease mechanisms, diagnosis/prognosis of pathologies, nutritional interventions and drug toxicity. Metabolic profiling is becoming increasingly important in identifying biomarkers of disease progression and drug intervention, and can provide additional information to support or aid the interpretation of genomic and proteomic data. With the new generation of postgenomic technologies, the paradigm in many biological fields has shifted to either top down systems biology approaches, aiming to achieve a general understanding of the global and integrated response of an organism or to bottom up modelling of specific pathways and networks using a priori knowledge based on mining large bodies of literature. Whilst metabolic profiling lends itself to either approach, using it in an exploratory and hypothesis generating capacity clearly allows new mechanisms to be uncovered.
Subluxation or dislocation of PCIOL is one of the complications of cataract operation in RP patients. This paper reports the presentation of PCIOL dislocation and subluxation and the management and outcome in 3 eyes of 2 RP patients. Two medical records of patients with RP who developed dislocated or subluxated PCIOL and subsequently underwent explantation of the dropped IOL were evaluated. Two patients had bilateral eye cataract operation done and had PCIOL implanted. Patient 1 developed left eye subluxated PCIOL inferiorly after 2 years of the cataract operation and right eye dislocated PCIOL anteriorly 4 years after cataract operation. Patient 2 develop right eye subluxated PCIOL inferiorly after 12 years of the cataract operation. Patient 1 with right eye dislocated PCIOL underwent intraocular lens (IOL) explantation and was left aphakic as her visual prognosis was poor due to advanced RP. The left IOL remained within the visual axis despite subluxation and no intervention has been done. Patient 2 with right eye subluxated PCIOL underwent IOL explantation and anterior chamber intraocular lens (ACIOL) implantation. ACIOL remained stable and visual acuity improved post-operation. Both the operations were uneventful. Post-operatively, there was no elevated intraocular pressure and no prolonged ocular inflammation, which required prolonged anti-inflammatory and no retinal detachment was seen. Both patient and surgeon should be aware of potential PCIOL subluxation or dislocation in RP. The presentation may be as late as more than a decade after the cataract operation.
Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.
The emergence of highly active antiretroviral therapy (HAART) has revolutionized the prognosis of HIV-infected patients. However, the extended use of HAART is associated with a disfiguring complication termed lipodystrophy, a disorder of body fat maldistribution causing peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). Lipoatrophy commonly affects the face, legs, buttocks and arm, whilst lipohypertrophy frequently favours the abdomen, breast and dorsocervical region. To our knowledge, we present only the second documented case in the literature of a labia majora lipohypertrophy in a HIV-positive patient receiving long-term HAART. The severity of labial abnormality caused significant physical and functional morbidities. Labiaplasty with dermolipectomy of the labia majora and excisional lipectomy of the mons pubis was successfully performed. At a 6-month follow-up, patient had no recurrence with resolution of symptoms and resumption of normal activities of daily living (ADL).
Lingual hamartoma is a rare finding of congenital midline posterior tongue mass. The lesion may be seen as a single anomaly or maybe associated with syndrome especially the Oral Facial Digital Syndrome (OFDS). Here, we report an otherwise normal and healthy two-month-old boy with a congenital midline base of tongue mass presented with snoring and episodic vomiting since the age of 1 month. Tumour excision from the area of foramen of caecum recovered a pinkish pedunculated tumour. Histopathology examination confirmed the diagnosis of leiomyomatous lingual hamartoma. Differential diagnosis, especially for midline tongue mass and other paediatric tongue lesions are discussed. We also discuss the epidemiology, histopathologic features, treatment and prognosis of lingual hamartoma based on the literature review.
BACKGROUND: Bone mineral density (BMD) is a lifetime marker of estrogen in a woman's body and has been associated with increased breast cancer risk. Nonetheless the actual association is still debatable. Furthermore, estrogen is very crucial in maintaining human bone density and gradually decreases over age. A systematic search was conducted to assess any association of BMD with breast cancer risk factors among premenopausal and postmenopausal women.
MATERIALS AND METHODS: Review identification was performed through databases searching on MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords used were "bone mineral density", "breast cancer", and "breast density".
RESULTS: A total of 19 articles showed variation with the majority of the studies focused on postmenopausal and a few focused on premenopausal women. Overall there was no concensus on effects.
CONCLUSIONS: An enormous effort is being undertaken by researchers to prove that BMD might be one of the significant risk factors for breast cancer.