Colorectal cancer in patient younger than 50-year-old in Kelantan: Two case reports.

Although young-onset colorectal cancer (CRC) is commonly linked to genetic predispositions such as Lynch syndrome, there has been an increasing trend in the prevalence of sporadic type youngonset CRC. We highlighted two cases of young patients diagnosed with CRC. Both patients came at the late stage of presentation with right sided colon tumour and local lymph nodes involvement. Loss of MLH1 expression with positive BRAF V600E was seen on immunohistochemistry staining. Additionally, they have no chronic disease or familial history of malignancy. The follow-up surveillance CT scan and the surveillance colonoscopy of case 1 showed no local recurrence and distant metastasis. However, another patient defaulted on the subsequent follow-up. In this report, we review the clinicopathological characteristics of these two cases and discuss the importance of the screening for the BRAF V600E and the four MMR proteins to characterise the sporadic and hereditary subgroups of young-onset CRC.

The journey of Malaysian external quality assurance program for general diagnostic histopathology.

International Academy of Pathology, Malaysian Division has initiated and run the external quality assurance program for general diagnostic histopathology since the year 2017. This article introduces the educational philosophy of this external quality assurance program and the technicalities in running such a national program. Challenges in ensuring the successful running of this program to gain wide acceptance by histopathology laboratories in Malaysia as well as experience in overcoming these challenges are detailed. This article charts the future direction of this external quality assurance program.

Expression of IGFBP-rP1 in ovarian and breast cancers in association with diabetes mellitus status.

INTRODUCTION: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM). MATERIALS AND METHODS: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient's demographic and clinicopathological data. RESULTS: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers. CONCLUSIONS: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.

Reduced Featured k-NN Classifier Model Optimal for Classification of Dengue Fever from Salivary Raman Spectra.

Current diagnostic methods based on nonstructural protein 1 (NS1) for dengue infection use blood as the medium and hence are invasive. Worry for blood infected diseases, pain from pricking, overcrowded public hospitals and ignorance are just a few of the causes for delayed diagnosis that contributes to mortality from dengue fever (DF). NS1 has also been reported in saliva, but sensitivity of detection is much lower than that of blood. If saliva is to be a medium, detection of NS1 requires a more specific and sensitive technique. In this study, we are exploiting the advantages of saliva and Surface Enhanced Raman Spectroscopy (SERS) to develop a non-invasive early detection method for DF. Significant features from Raman spectra of saliva samples of dengue suspected patients and healthy volunteers were extracted with Principal Component Analysis (PCA) and served as input to k-Nearest Neighbour (k-NN) for classification. Cumulative Percentage Variance (CPV) is the criterion for feature extraction. Two k-NN distance rules (Cosine and Manhattan) combined with k-values ranging from 3 to 17 were varied to obtain an optimal k-NN classifier. Then, performance of the different k-NN classifier models is benchmarked against Panbio Dengue Early ELISA and SD BIOLINE Dengue Duo technique from the clinical laboratory. The finding is encouraging with the best performance achieved, 82.14% for accuracy, 85.71% for sensitivity and 78.57% for specificity.

Optimal ELM-RBF model and SERS Analysis of Saliva for Classification of NS1.

Extreme Learning Machine (ELM) with Radial Basis Function (RBF) Kernel has demonstrated strong capability in pattern recognition and classification problems. NS1 is a biomarker for flavivirus related diseases, where current detection methods are serum based and hence invasive. Our previous work has captured NS1 molecular fingerprint in saliva using Surface Enhanced Raman Spectroscopy (SERS) that could amount to non-invasive detection method. SERS is an improved Raman spectroscopic technique, which can amplify spectral intensity by 103 to l07 times, to yield usable spectra of low concentration NS1 in saliva. The spectra produced contain 1801 features for each of the 284 samples collected. Principal Component Analysis (PCA) transforms a high dimensional data to a lower dimension principal components (PCs), at no sacrifice of important information of the original data. Both termination criteria of PCA and kernel parameters of ELM have effect on performance of the classifier models. This paper aims to unravel an optimal ELM-RBF classifier model for classification of NS1 salivary SERS spectra. Performance of a total of 864 classifier models are examined and compared in terms of [accuracy, kappa, precision, sensitivity and specificity]. Results show that CPV- and EOC-ELM-RBF classifier models are on par and outperform the Scree-ELM-RBF classifier models.

Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients.

Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available single-nucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.

Recurrent glossal leiomyoma.

Oral leiomyomas are rare benign tumour of smooth muscle. The first case of oral leiomyoma was reported by Blanc in 1884 and since then more cases has been published following advancement in immunohistochemical study. This tumour has an excellent prognosis and recurrences are extremely rare. We report a case of a recurrent glossal leiomyoma in a patient with HIV infection and the lesion recurred one year after the first excision.

The inference of breast cancer metastasis through gene regulatory networks.

Understanding the mechanisms of gene regulation during breast cancer is one of the most difficult problems among oncologists because this regulation is likely comprised of complex genetic interactions. Given this complexity, a computational study using the Bayesian network technique has been employed to construct a gene regulatory network from microarray data. Although the Bayesian network has been notified as a prominent method to infer gene regulatory processes, learning the Bayesian network structure is NP hard and computationally intricate. Therefore, we propose a novel inference method based on low-order conditional independence that extends to the case of the Bayesian network to deal with a large number of genes and an insufficient sample size. This method has been evaluated and compared with full-order conditional independence and different prognostic indices on a publicly available breast cancer data set. Our results suggest that the low-order conditional independence method will be able to handle a large number of genes in a small sample size with the least mean square error. In addition, this proposed method performs significantly better than other methods, including the full-order conditional independence and the St. Gallen consensus criteria. The proposed method achieved an area under the ROC curve of 0.79203, whereas the full-order conditional independence and the St. Gallen consensus criteria obtained 0.76438 and 0.73810, respectively. Furthermore, our empirical evaluation using the low-order conditional independence method has demonstrated a promising relationship between six gene regulators and two regulated genes and will be further investigated as potential breast cancer metastasis prognostic markers.

Combined assessment of TGF-beta-1 and alpha-fetoprotein values improves specificity in the diagnosis of hepatocellular carcinoma and other chronic liver diseases in Malaysia.

Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.

Evaluation of polymerase chain reaction (PCR) method and hybrid capture II (HCII) assay for the detection of human papillomavirus in cervical scrapings.

In order to investigate the reliability of detecting HPV DNA in cervical smears, we compared the performance of nested MY/GP PCR and FDA approved-Hybrid Capture II (HCII) using clinical cervical scrapings from 40 patients. It was found that PCR was more sensitive (81.8%) in comparison to HCII (36.4%) in detecting HPV although specificity of HCII was much higher (96.6%) than PCR (58.6%). The Negative Predictive Value (NPV) of both the techniques were quite similar but Positive Predictive Value (PPV) of HCII was much higher (80.0%) compared to PCR (42.9%). While the HCII method showed good specificity for HPV detection, its lack of sensitivity as compared to PCR may be a drawback for diagnostic use.

Research on cancer diagnosis in Malaysia: current status.

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.

Adjuvant treatment in colorectal cancer. Experience from a referral center in eastern peninsular Malaysia.

BACKGROUND: Colorectal cancer is one of the most common malignancies in the West, but in Asia the incidence is low. However in Malaysia, colorectal cancer is increasing with a reported figure of 15% of all cancer cases. Adjuvant chemo and radiotherapy are now more frequently used in such patients. The present retrospective analysis was performed to document the effect of such therapy among patients with colorectal cancer in Malaysia. MATERIALS AND METHODS: This is a retrospective study on the use of adjuvant treatment in colorectal cancers. Patients with histopathological evidence of risk factors were subjected to adjuvant radiotherapy and/or chemotherapy. Cancers confined to rectum and rectosigmoid were subjected to pelvic radiotherapy to a tumor dose of 45 Gy in 20 fractions over 4-week period. 5-flurouracil based chemotherapy was predominantly offered for colonic cancers. RESULTS: One hundred thirty patients with colorectal cancers received adjuvant treatment with a median age of 58 years (range 22-76 years). The male to female ratio was 1.4:1. There were 76% Malays, 19% Chinese, 2% Indians and 3% Siamese subjects in this study. Modified Dukes' stage B2 (28%) and C (38%) constituted the majority, which were distributed in rectum (40%), rectosigmoid (19%), and in the remaining colon (41%). Thirty-one patients received 5-fluorouracil with folinic acid based regime and 35 patients received 5-fluorouracil with levamisole based regimen. Locoregional radiotherapy was offered to 56 (43%) patients. Following treatment, the 2-year actuarial survival was 28% and 54% in colon and rectum cancer respectively. CONCLUSIONS: This study showed that colorectal cancer is not infrequent among Malays in this region and rectal cancers had better survival than the colonic cancers.

Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform expression in ectopic acromegaly.

Bronchial endocrine neoplasms causing acromegaly due to ectopic production of growth hormone (GH)-releasing hormone (GHRH) have been reported. We describe the case of a 39-year-old man with clinical and biochemical acromegaly. Magnetic resonance imaging revealed an enlarged pituitary, which was confirmed histologically to harbour somatotroph hyperplasia. Further investigations identified a circumscribed central mass in the right lung which was surgically resected and histologically confirmed to be an endocrine tumour with strong immunopositivity for GHRH, synaptophysin and chromogranin; the lesion also exhibited mild positivity for peptide YY, calcitonin gene-related peptide (CGRP), glucagon-like peptide (GLP)-1, corticotrophin-releasing hormone (CRH), tyrosine hydroxylase, vasoactive intestinal peptide (VIP) and enkephalin. S100 protein was identified in stellate cells surrounding nests of epithelial tumour cells. The MIB-1 antibody labelled about 10% of the tumour cells. We established that the tumour not only produced GHRH but the GHRH-receptor (GHRH-R) as well. GHRH and GHRH-R mRNA were identified and the latter was characterized as two variants, a full-length transcript and a truncated splice variant that has been described in human pituitary somatotroph adenomas. We suggest that GHRH expression by this tumour and the presence of its receptor may be responsible for enhanced growth. The expression of a truncated splice variant that is unable to transduce GHRH signalling may be implicated in the less aggressive behaviour of well-differentiated endocrine tumours that produce GHRH compared with small-cell lung carcinomas that are very responsive to GHRH growth stimulation.

Kimura's disease: a report of three cases with a brief review of literature.

Kimura's disease (KD) is an uncommon chronic inflammatory condition of unknown aetiology involving subcutaneous tissue, presenting as a tumor like lesion with a predilection for the head and neck region. Clinically it is often confused with parotid tumor with lymph node metastasis. It is difficult to diagnose before tissue biopsy. Fine needle aspiration cytology has only limited value. Unless the pathologists are aware of this entity, it might be misdiagnosed. Surgery, radiotherapy and steroid therapy have been tried but none is proved best and recurrence is common. Three cases of KD seen in our hospital and the problems encountered in them are presented.

Malignant paraganglioma of frontoethmoidal region.

Nonchromaffin paragangliomas are unusual tumours arising from widely distributed paraganglionic tissues probably of neural crest origin. In the head and neck region they are usually seen as carotid body or jugulotympanic tumours. Other rarely reported sites in the head and neck region are the orbit, nose and larynx. This report deals with a case of sinonasal paraganglioma which was initially treated with surgery and radiotherapy. Twenty two years later the tumour recurred and showed a rapid growth due to malignant transformation which we believe is late effect of radiotherapy. The clinical features, histopathology and role of radiotherapy in sinonasal paragangliomas together with a review of the medical literature have been discussed.

Teratocarcinosarcoma of the nasal cavity and ethmoid.

Sinonasal teratocarcinosarcoma is very unusual malignant neoplasm histologically consisting of an epithelial element and one or more mesenchymal components. This is a report of teratocarcinosarcoma, in a 74-year-old male, involving the right nasal cavity and ethmoids with intracranial extension. The tumour was totally resected via the craniofacial approach and the patient was given post-operative chemotherapy. Extensive tumour necrosis, rapid growth and local destruction are the prominent features of this tumour. The clinical presentation, pathological features and clinical course of this rare malignancy are discussed with a review of the literature.

Multiple polypoid endometriosis--a rare complication following withdrawal of gonadotrophin releasing hormone (GnRH) agonist for severe endometriosis: a case report.

A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. We postulate that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. We believe this is the first report of this complication following use of GnRH analogue.

Endometrial amoebiasis.

A case of endometrial infection by Entamoeba histolytica is described in an elderly lady who presented with profuse vaginal discharge and was clinically misdiagnosed as endometrial carcinoma.

Cerebrotendinous xanthomatosis with cholestanolaemia--involvement of five individuals in a Malay family.

Cerebrotendinous xanthomatosis (CTX), a rare inherited lipid storage disease is due to a defect in bile acid metabolism. Involvement of five members of a family is presented. The clinical features, laboratory and pathologic findings are discussed. Tendinous and tuberous xanthomatosis, bilateral cataracts, cerebral impairment and raised serum cholestanol are the salient features. We believe this is the first report of CTX in Malaysia.