Publications by authors named "Andee Dzulkarnaen Zakaria"

31 Publications

Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins.

Genes (Basel) 2021 Sep 20;12(9). Epub 2021 Sep 20.

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.

Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.

Results: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes- and -which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes- and -harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.

Conclusion: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.
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http://dx.doi.org/10.3390/genes12091448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471947PMC
September 2021

Traumatic Neck Injury: An Accidental Impalement by a Needlefish.

Wilderness Environ Med 2021 Aug 31. Epub 2021 Aug 31.

Borneo Marine Research Institute, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.

Encounters between marine animals and humans can result in critical injury and fatal complications. We highlight a 20-y-old male who sustained a penetrating injury to the neck as a result of impalement by needlefish (Tylosurus sp) while snorkeling. He sustained a penetrating injury in the posterior triangle of the neck. On presentation, he was stabilized and received empirical antibiotics, analgesia, and antitetanus toxoid injection before being transferred to a tertiary center. On presentation to the tertiary hospital, the patient was hemodynamically stable with no clinical evidence of injury to surrounding neck structures, and this was confirmed using computed tomography. The patient underwent local wound exploration and retrieval of the needlefish beak under general anesthesia. The wound was left open to heal by secondary intention. The patient was discharged with oral antibiotics and went on to make a complete recovery.
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http://dx.doi.org/10.1016/j.wem.2021.07.006DOI Listing
August 2021

Conversion Rate and Risk Factors of Conversion to Open in Laparoscopic Appendicectomy.

Ann Coloproctol 2021 Aug 18. Epub 2021 Aug 18.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Purpose: Laparoscopic appendicectomy (LA) has several advantages over conventional open appendicectomy (OA). However, about 5% to 10% of LA patients still need to be converted to open surgery. Identifying risk factors that contribute to conversion to OA allows for early identification of patients who may benefit from primary OA. This study aimed to determine the conversion rate of LA to OA and to identify its associated risk factors among patients with acute or perforated appendicitis.

Methods: A retrospective review of medical records was performed among patients with acute or perforated appendicitis who underwent LA between December 2015 and January 2017. With the use of multivariable logistic regression analyses, the predictors of conversion from laparoscopic to OA were investigated.

Results: Out of 120 patients, 33 cases were converted to OA which gives a conversion rate of 27.5%. Among 33 patients who were converted to OA, 27 patients (81.8%) had perforated appendix, while in the LA group, perforated appendix cases consisted of 34.5% (P<0.001). Histopathology of the appendix was the predictor of conversion from LA to OA (adjusted odds ratio, 8.82; 95% confidence interval, 3.13-24.91; P<0.001).

Conclusion: The result from our study shows that the overall conversion rate for the study period was high. Patients with perforated appendicitis had a higher risk of conversion to OA. Therefore, preoperative diagnosis of perforated appendicitis may be paramount in predicting conversion to OA.
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http://dx.doi.org/10.3393/ac.2020.00437.0062DOI Listing
August 2021

BRAF V600E and Mismatch Repair Proteins Expression in Sporadic Young-onset Colorectal Cancer in Kelantan, Malaysia.

Oman Med J 2021 Jul 26;36(4):e284. Epub 2021 Jul 26.

Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

Objectives: We sought to determine the immunohistochemistry expression of mismatch repair (MMR) and BRAF V600E proteins in sporadic young-onset colorectal cancer (CRC) and their association with clinicopathological features in the Kelantan population.

Methods: This was a cross-sectional study of sporadic young-onset CRC over 11 years from 1 January 2006 to 31 December 2017 in Kelantan. Formalin-fixed paraffin-embedded tissue blocks were immunohistochemically stained with antibodies for MMR (MLH1, MSH2, MSH6, and PMS2) and BRAF V600E. These expressions were correlated with clinicopathological parameters.

Results: Our patient sample included 31 patients with a mean age of 31.5 years. More than half (61.3%) of the patients were women. The majority presented with abdominal pain (41.9%), and 71.0% had a tumor located on the right side of the colon, with 83.9% being moderately differentiated adenocarcinoma. The majority of patients presented at stage IV (54.8%). The most frequent pattern was all MMR protein expressions, which constituted patients in the microsatellite stable group (64.5%). Nine (29.0%) were microsatellite instability (MSI-high), and two (6.5%) were MSI-low. Positive BRAF V600E expression was observed in 83.9% of patients. Only histopathological subtypes revealed a significant association with BRAF V600E positive expression ( 0.015).

Conclusions: The majority of sporadic young-onset CRC presented with abdominal pain and advanced cancer stage. Most were microsatellite stable, and most cases showed positive expressions in all MMR markers and BRAF V600E by immunohistochemistry method. This finding will pave the way for further research on this disease.
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http://dx.doi.org/10.5001/omj.2021.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311123PMC
July 2021

Colorectal cancer and potential predictors of never screened for faecal occult blood test: a narrative review.

J Public Health Res 2021 Aug 4. Epub 2021 Aug 4.

Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Cheras, Kuala Lumpur.

Colorectal cancer (CRC) is a major public health threat. Therefore, CRC screening uptake has been a focus with the established precancerous lesion and the strong association of early detection with staging and survival of the disease. However, CRC screening is relatively low in many countries. This article briefly discussed the current situation of CRC, recommendations, and current uptake of CRC screening in various countries. Besides that, this article also highlights the potential factors that help to predict the CRC screening uptake worldwide. Identification of those factors could guide policymakers to develop an effective strategy to improve the CRC screening uptake and ultimately improve the health outcome of the population.
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http://dx.doi.org/10.4081/jphr.2021.2377DOI Listing
August 2021

Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen.

Asian Pac J Cancer Prev 2021 Apr 1;22(4):1319-1324. Epub 2021 Apr 1.

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia.

Background: Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers.

Aim: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen.

Methods: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients' recurrence risk.

Results: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes.

Conclusion: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.
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http://dx.doi.org/10.31557/APJCP.2021.22.4.1319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325143PMC
April 2021

Re: Perforated descending colon adenocarcinoma manifesting as necrotizing fasciitis.

ANZ J Surg 2021 04;91(4):763-764

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

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http://dx.doi.org/10.1111/ans.16536DOI Listing
April 2021

Empyema thoracis presented as giant back abscess.

Radiol Case Rep 2021 May 24;16(5):1061-1064. Epub 2021 Feb 24.

Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.

Empyema thoracis (ET) is defined as pus in the pleural space, either localized or involving the entire pleural cavity, due to diverse etiologies. In severe form, it may infiltrate the extrapulmonary region. Clinical guideline describes 3 stages of parapneumonic effusion before developing into an ET, namely the exudative stage, the fibrinopurulent stage, and the organizing/late stage. We highlight a 59-year-old gentleman who presented a back swelling masquerading as a deep-seated abscess, in which the diagnosis of ET had not been established early. The principles of treatment are treating the underlying condition such as pneumonia, pleural drainage and debridement, full re-expansion of the collapsed lung by performing chest physiotherapy, and improving nutrition. ET is a condition with a dynamic process due to diverse etiologies, either localized or involving the entire pleural cavity. The gold standard in diagnosing ET is the pleural aspiration of fluid from the pleural space, whereas the management of ET may include non-surgical and/or surgical treatments based on the basic principles of ET treatment.
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http://dx.doi.org/10.1016/j.radcr.2021.02.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917453PMC
May 2021

Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer.

Sci Rep 2021 02 3;11(1):2925. Epub 2021 Feb 3.

UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia.

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.
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http://dx.doi.org/10.1038/s41598-021-82465-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859180PMC
February 2021

Perforated caecal mass: benign or malignant?

ANZ J Surg 2021 Jul 22;91(7-8):1620-1622. Epub 2020 Dec 22.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

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http://dx.doi.org/10.1111/ans.16508DOI Listing
July 2021

Trapped heart in heavily calcified pericardium.

Oxf Med Case Reports 2020 Oct 23;2020(10):omaa083. Epub 2020 Oct 23.

Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.

Constrictive pericarditis is a disabling disease of the heart, which causes cardiac diastolic dysfunction. We present a case of a 44-year-old gentleman with a history of blunt chest trauma who presented with constrictive pericarditis with right-sided heart failure. Imaging studies revealed a calcified pericardium. He underwent an uneventful pericardiectomy. Calcification is common yet rare if it involves the pericardium. It normally occurs following fibrosis and adhesion which are associated with the chronicity of the disease, hence creating more challenge to the operating surgeon in the pericardiectomy procedure.
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http://dx.doi.org/10.1093/omcr/omaa083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583414PMC
October 2020

The Use of M2-Pyruvate Kinase as a Stool Biomarker for Detection of Colorectal Cancer in Tertiary Teaching Hospital: A Comparative Study.

Ann Coloproctol 2020 Dec 18;36(6):409-414. Epub 2020 Sep 18.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

Purpose: Guaiac fecal occult blood test (gFOBT) has been the standard for colorectal screening but it has low sensitivity and specificity. This study evaluated the use of fecal tumor M2-pyruvate kinase (M2-PK) for detection of colorectal cancer and to compare with the current surveillance tool; gFOBT in symptomatic adult subjects underwent colonoscopy.

Methods: Stool samples were collected prospectively from symptomatic adults who had elective colonoscopy from September 2014 to January 2016 and were analyzed with the ScheBo M2-PK Quick test and laboratory detection of fecal hemoglobin.

Results: The results were correlated to the colonoscopy findings and/or histopathology report. Eighty-five subjects (age of 56.8 ± 15.3 years [mean ± standard deviation]) were recruited with a total of 17 colorectal cancer (20.0%) and 10 colorectal adenoma patients (11.8%). The sensitivity of M2-PK test in colorectal cancer detection was higher than gFOBT (100% vs. 64.7%). M2-PK test had a lower specificity when compared to gFOBT (72.5% vs. 88.2%) in colorectal cancer detection. The positive and negative predictive values were 47.2% and 100% for M2-PK test and 57.9% and 90.9% for gFOBT.

Conclusion: Fecal M2-PK Quick test has a high sensitivity for detection of colorectal cancer when compared to gFOBT, making it the potential choice for colorectal tumor screening biomarker in the future.
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http://dx.doi.org/10.3393/ac.2020.08.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837393PMC
December 2020

Vanek's tumor causing ileoileal intussusception in a middle-aged man.

Oxf Med Case Reports 2020 Jul 24;2020(7):omaa050. Epub 2020 Jul 24.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Intestinal obstruction is a common surgical emergency requiring urgent intervention. Small bowel obstruction secondary to intussusception is rarely encountered especially when inflammatory fibroid polyp (IFP) is the lead point. A 41-year-old gentleman with intestinal intussusception secondary to IFP presented to us with a classic symptom of intestinal obstruction. Computed tomography revealed a target or sausage-shaped soft tissue mass with a layering effect, which was confirmed by intraoperative findings. Histopathology was consistent with IFP and supported by immunoreactivity of CD34 and negative immunostaining for CD117. He recovered without any surgical complication or recurrence. Even intussusception can be managed via non-surgical technique in children; surgery is the mainstay of treatment in adults.
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http://dx.doi.org/10.1093/omcr/omaa050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376978PMC
July 2020

Letter to: Local anaesthesia for haemorrhoidal rubber band ligation reduces immediate post-operative recovery time and use of opioid analgesia.

ANZ J Surg 2020 06;90(6):1217

Department of Biomedical Science and Therapeutic, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia.

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http://dx.doi.org/10.1111/ans.15920DOI Listing
June 2020

Predictors of early postoperative hypocalcemia after total parathyroidectomy in renal hyperparathyroidism.

Ann Surg Treat Res 2020 Jan 30;98(1):1-6. Epub 2019 Dec 30.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia.

Purpose: Patients with secondary hyperparathyroidism are at high risk for developing postoperative hypocalcemia. However, there are limited data regarding predictors of postoperative hypocalcemia in renal failure patient with secondary hyperparathyroidism. This study aimed to determine the clinical presentations of renal hyperparathyroidism and the predictors of early postoperative hypocalcemia after total parathyroidectomy.

Methods: Data of patients with renal hyperparathyroidism who underwent total parathyroidectomy between January 2007 to December 2014 were reviewed retrospectively. Patients were divided into 2 cohort groups according to their serum calcium levels within 24 hours of parathyroidectomy: the hypocalcemia group (calcium levels of 2 mmol/L or less), and the normocalcemia group (calcium levels more than 2 mmol/L). With the use of multivariable logistic regression analyses, the predictors of early postoperative hypocalcemia after total parathyroidectomy in patients with renal hyperparathyroidism were investigated.

Results: Among 68 patients, 56 patients (82.4%) were symptomatic preoperatively. Fifty patients (73.5%) presented with bone pain and 14 patients (20.6%) had muscle weakness. Early postoperative hypocalcemia occurred in 25 patients (36.8%). Preoperative alkaline phosphatase level was the predictor of early postoperative hypocalcemia (adjusted odds ratio, 1.004; 95% confidence interval, 1.001-1.006; P = 0.002).

Conclusion: Results from our study show that most of the patients with renal hyperparathyroidism were symptomatic preoperatively and the most common clinical presentations were bone pain and muscle weakness. The significant predictor of early postoperative hypocalcemia after total parathyroidectomy was the preoperative alkaline phosphatase levels.
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http://dx.doi.org/10.4174/astr.2020.98.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940428PMC
January 2020

Intestinal knot in acute Meckel's diverticulitis.

BMJ Case Rep 2019 Nov 24;12(11). Epub 2019 Nov 24.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

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http://dx.doi.org/10.1136/bcr-2019-232611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887436PMC
November 2019

Contribution of Genetic Polymorphisms of Inflammation Response Genes on Sporadic Colorectal Cancer Predisposition Risk in Malaysian Patients - A Case Control Study.

Asian Pac J Cancer Prev 2019 06 1;20(6):1621-1632. Epub 2019 Jun 1.

Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia.

AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308 G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560 study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF – α 308 G>A contribute to a significantly higher risk among male and female who are more than 50 years and for smokers in this population. Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308 G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic predisposition factors for CRC in Malaysian population.
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http://dx.doi.org/10.31557/APJCP.2019.20.6.1621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021613PMC
June 2019

Collapsed wall: destructive and reconstructive surgery of anterior abdominal wall tumour in a young girl.

J Surg Case Rep 2019 Feb 8;2019(2):rjy345. Epub 2019 Feb 8.

Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia.

Natural history of abdominal wall soft tissue sarcoma is still poorly understood due to its rarity. In unpublished data of our institution, only seven cases of abdominal wall soft sarcoma with ICD-10 coding of 49.4 were found for past 10 years. We illustrate a case of juvenile fibrosarcoma of anterior abdominal wall. This is a case of young girl with anterior abdominal wall tumour, underwent wide local excision with immediate reconstruction. There are few options of surgical treatment for this case, but which is the best. It is always a challenge in managing young patient with giant abdominal wall defect in view of long term effect namely weakened abdominal wall, pregnancy related issue and risk of herniation and surgical site recurrence as well.
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http://dx.doi.org/10.1093/jscr/rjy345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368141PMC
February 2019

Single-nucleotide polymorphisms and mRNA expression of influence treatment response in triple negative breast cancer patients undergoing chemotherapy.

J Genet 2018 Dec;97(5):1185-1194

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 () is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), 142 C>G, 4326 C>G and 4360 A>G, and mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of may be useful biomarkers to predict chemotherapy response in TNBC patients.
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December 2018

Postoperative major surgery patients developing silent deep vein thrombosis: A prospective observational study.

J Vasc Nurs 2018 Dec 6;36(4):173-180. Epub 2018 Aug 6.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia. Electronic address:

Surgical patients are at high risk for developing deep vein thrombosis (DVT). There are many reports concerning DVT, but little is known about silent deep vein thrombosis (sDVT). This study aimed to determine the incidence of sDVT. Secondary objective is to identify the associated factors for the use of DVT prophylaxis and Caprini risk scores among major surgery patients. This prospective observational study involved postoperative surgical patients who are at risk of developing sDVT. The Caprini risk-assessment scores were calculated, and each subject had a preoperative and postoperative compression ultrasound complemented by duplex venous ultrasonography of deep venous system. No patient from the study experienced sDVT. There were significant associations between Caprini risk score group (odds ratio, 8.16; 95% confidence interval [CI], 1.01-68.74; P = .016) and the use of central venous catheter (odds ratio, 6.34; 95% CI, 1.62-24.80; P = .008) with DVT prophylaxis. Interestingly, the use of central venous catheter resulted in more than four-point increment of Caprini risk scores (mean increment, 4.19; 95% CI, 3.16-5.21; P < .001). Besides that, age was also significantly associated with Caprini risk scores (β coefficient, 0.06; 95% CI, 0.02-0.11). Result from our study shows that the sDVT was nonexistent in this study setting. High-Caprini risk score group and the presence of central venous catheter were the significant predictor factors for the use of DVT prophylaxis. Significant predictor factors for Caprini risk scores were age and the presence of central venous catheter.
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http://dx.doi.org/10.1016/j.jvn.2018.07.001DOI Listing
December 2018

Giant Preputial Calculus: The First Reported Case in Malaysia.

Case Rep Surg 2018 18;2018:4606259. Epub 2018 Sep 18.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

Preputial calculus is a relative surgical rarity. It usually happens in elderly men with poor hygiene and uncircumcised penis complicated with phimosis. In the paediatric group, it is usually secondary to phimosis and other urologic and/or neurologic anomalies. Surgical treatment is the mainstay of treatment. Herein, we report a 27-year-old gentleman with preputial stone presented with obstructive uropathy and was successfully treated with surgical intervention. To the best of our knowledge, this is the first reported case of the largest preputial stone in Malaysia.
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http://dx.doi.org/10.1155/2018/4606259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167587PMC
September 2018

Prospective diagnostic study on the use of narrow-band imaging on suspicious lesions during colonoscopy examination.

Asian J Endosc Surg 2018 Nov 8;11(4):318-324. Epub 2018 Feb 8.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.

Introduction: Colonoscopy is the gold standard to detect colorectal neoplasm. Narrow-band imaging (NBI) has a good diagnostic accuracy to differentiate between neoplastic and non-neoplastic colorectal lesions. This study explores the diagnostic validity of NBI colonoscopy as well as its associated factors related to neoplastic and non-neoplastic colorectal lesions.

Methods: This study enrolled 100 patients in a single-center tertiary teaching hospital. Patients presented for screening colonoscopy, and those with suspicious colorectal lesions were included in this study. During colonoscopy, the most suspicious lesion in each patient was analyzed using the NBI system based on Sano's classification. Each lesion was biopsied for histopathological analysis, the gold standard. Endoscopic images were captured electronically. The sensitivity, specificity, and diagnostic accuracy of NBI colonoscopy were assessed. Other associated factors related to neoplastic and non-neoplastic lesions were analyzed accordingly.

Results: The sensitivity and specificity of the NBI were 88.2% and 71.9%, respectively. The area under the receiver-operator curve was 0.801, indicating that NBI has a good ability to differentiate between disease and non-disease. There are significant associations between histopathological examination outcomes and both presenting symptoms, especially weight loss, and lesion site, even after other variables were controlled (P < 0.05).

Conclusion: The NBI system in colonoscopy was capable of distinguishing neoplastic from non-neoplastic colorectal lesions. It indicates an acceptable level of agreement with histopathology, the gold standard. However, the role of NBI in screening and surveillance in Malaysia still needs further evaluation and exploration.
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http://dx.doi.org/10.1111/ases.12463DOI Listing
November 2018

Rare case of primary leiomyosarcoma of sigmoid mesocolon.

BMJ Case Rep 2017 Sep 15;2017. Epub 2017 Sep 15.

Department of Surgery, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

We experienced a rare case of primary leiomyosarcoma of sigmoid mesentery. A 45-year-old woman was presented to us with left iliac fossa mass and discomfort for 4-month duration. CT scan of abdomen and pelvis revealed a huge mass 14 cm×14 cm×16 cm occupying left iliac fossa mimicked having a large left ovarian carcinoma. She was subsequently planned for elective total abdominal hysterectomy and bilateral salpingo-oophorectomy by gynaecology team. During laparotomy, a huge mass was revealed arising from sigmoid mesentery invaded to the left lower ureter. Curative resection was done and pathological findings show the tumour being leiomyosarcoma with immunohistochemistry tests on caldesmon, desmin, smooth muscle actin and CD34 reagent all positive. Clinicopathological and literature review of this rare primary leiomyosarcoma of mesocolon was discussed in our case presentation.
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http://dx.doi.org/10.1136/bcr-2017-219826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614005PMC
September 2017

Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery

Asian Pac J Cancer Prev 2017 07 27;18(7):1821-1825. Epub 2017 Jul 27.

Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Sabah, Malaysia. Email:

Background: Anastomotic leaks in colorectal surgery results in a high morbidity and mortality rate. Serum procalcitonin levels is known as a sensitive and specific marker of sepsis and could be use as a marker for early detection of a leak allowing early intervention. It may help a clinician decide to perform a CT scan even earlier especially when the diagnosis of a leak is uncertain. The aim of this study is to determine whether serum procalcitonin is a good predictor of anastomotic leak in colorectal surgery. Methodology: Between July 2014 until October 2015, 70 patients undergoing colorectal surgery were prospectively analyzed in a single-center tertiary teaching hospital. Demographic and surgical data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72 hours) postoperatively. During the postoperative period, the patients were observed in the ward for features of anastomotic leak and if present, it was managed accordingly. The primary outcome was to prospectively determine an association between serum procalcitonin levels and an anastomotic leak in patients who underwent colorectal surgery with a primary anastomosis. Result: The rate of anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3 patients). A rise in serum procalcitonin was statistically significant among patients with anastomotic leak. The optimal procalcitonin cut-off level at postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85% specificity, 23% positive predictive value and 100% negative predictive value. Nevertheless, none of the variables showed statistical significance with an anastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to help diagnose anastomotic leak in colorectal surgery. Our study has shown that a level of 5 times beyond normal is statistically significant and a value of more than 5.27 ng/mL is confirmatory of a leak.
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http://dx.doi.org/10.22034/APJCP.2017.18.7.1821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648385PMC
July 2017

Rare and unusual case of polyarteritis nodosa involving the gastrointestinal tract leading to bowel gangrene.

BMJ Case Rep 2017 Jan 6;2017. Epub 2017 Jan 6.

Department of Surgery, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis preferentially targeting medium-sized arteries and not related with glomerulonephritis or small vessel involvement. Clinical manifestations of PAN are multisystem. The gastrointestinal, renal, cardiac, musculoskeletal, skin and central nervous systems may be involved. The aetiology remains unknown, and the ensuing vasculitis may lead to aneurysm formation and thrombosis in any organs of the body with resultant ischaemia. PAN of the intestines is a relatively common manifestation of this disease but rarely causes bowel ischaemia resulting in necrosis. Here we report a case of a young Chinese patient who presented with an acute abdomen requiring surgery and made good recovery post operatively. He remains free of symptoms while on steroid therapy.
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http://dx.doi.org/10.1136/bcr-2016-217865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256521PMC
January 2017

Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration.

Case Rep Surg 2016 11;2016:7615029. Epub 2016 Oct 11.

Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.

We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour.
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http://dx.doi.org/10.1155/2016/7615029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078647PMC
October 2016

Effect of Tualang honey on the anastomotic wound healing in large bowel anastomosis in rats-A randomized controlled trial.

BMC Complement Altern Med 2016 Jan 23;16:28. Epub 2016 Jan 23.

Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150, Malaysia.

Background: Honey has long been used for the treatment of number of ailments and diseases including surgical wounds. Current study evaluates the effectiveness of Tualang honey (TH) for large bowel anastomotic healing in Wistar rats.

Methods: Thirty male Wistar rats were given a 3 centimeter infra-umbilical laparotomy wound, in`flicted on their abdomen. The colonic transection was performed at 5 cm distal to caecum, with end to end anastomosis of colon segment. They were divided into two groups. Group I was fed with standard rat chow and water. Meanwhile, Group II apart from standard feed, was also given TH 1.0 g/kg every morning until day seven post operatively. Afterwards, anastomotic bursting pressures were measured and histopathological examination on the anastomosis line was performed with light microscopes. The data from two groups were analyzed by Independent paired t test for continuous variables.

Results: It was found that the tensile strength of colon anastomosis (95 % CI; p = <0.001) and the histopathological study including fibroblast count (p = <0.001) and inflammatory cells (p = 0.002) showed statistically significant difference in the favor of TH-treated group. Meanwhile, neovascularization formation was not statistically significant (p = 0.807); however, the overall count in the TH group was high.

Conclusion: Oral treatment with TH enhances anastomotic wound healing by increasing the number of fibroblasts and by decreasing inflammatory cells leading towards increased wound strength.
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http://dx.doi.org/10.1186/s12906-016-1003-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724403PMC
January 2016

Prevalence of Helicobacter pylori cagA, babA2, and dupA genotypes and correlation with clinical outcome in Malaysian patients with dyspepsia.

Turk J Med Sci 2015 ;45(4):940-6

Background/aim: The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes.

Materials And Methods: H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-positive patients.

Results: The positive rates for cagA, babA2, and dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%, respectivel cagA was more prevalent in Indians (39.7%), babA2 was more prevalent in Malays (39.5%), and dupA detection occurred more frequently in both Indians and Malays and at the same rate (37.5%). The Chinese inhabitants had the lowest prevalence of the three genes. Nonulcer disease patients had a significantly higher distribution of cagA (76.7%), babA2 (74.4%), and dupA (75.0%). There was no apparent association between these virulence genes and the clinical outcomes.

Conclusion: The lower prevalence of these genes and variations among different ethnicities implies that the strains are geographically and ethnically dependent. None of the virulence genes were knowingly beneficial in predicting the clinical outcome of H. pylori infection in our subjects.
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http://dx.doi.org/10.3906/sag-1409-77DOI Listing
October 2015

Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening.

Asian Pac J Cancer Prev 2015 ;16(9):3767-71

Department of Paediatric, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia E-mail :

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.

Materials And Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.

Results: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.

Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.
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http://dx.doi.org/10.7314/apjcp.2015.16.9.3767DOI Listing
February 2016
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