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Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery

Hayati F, Mohd Azman ZA, Nasuruddin DN, Mazlan L, Zakaria AD, Sagap I

Asian Pac J Cancer Prev, 2017 07 27;18(7):1821-1825.
PMID: 28749112

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.
Fulltext The effect of pre-endoscopy maltodextrin beverage on gastric residual volume and patient's well-being: a randomised controlled trial

Zulkifli MF, Md Hashim MN, Zahari Z, Wong MP, Syed Abd Aziz SH, Yahya MM, et al.

Sci Rep, 2023 Nov 16;13(1):20078.
PMID: 37973795 DOI: 10.1038/s41598-023-47357-5

Prolonged fasting prior to oesophagogastroduodenoscopy (OGDS) could be noxious to patients' well-being. Strict fasting protocol has been used prior to OGDS with the concern of reduced visibility or suboptimal endoscopic assessment. Maltodextrin beverages were also commonly used as the pre-operative carbohydrate loading in enhanced recovery after surgery (ERAS) protocol. Our study aimed to look for the effects of maltodextrin beverage 2 h before OGDS on gastric residual volume and patient's well-being scores. This was a single-blinded, stratified randomised controlled trial, comparing control group (A, received 400 ml of plain water) and carbohydrate loading group (B, received 400 ml of Carborie). The primary objectives were to measure the gastric residual volume (GRV) and patient's well-being scores using visual analogue scale (VAS) scores for hunger, thirst, anxiety, tiredness and general discomfort. Of 80 randomised patients, 78 completed the study (38 received plain water and 40 Carborie). The median (IQR) GRV was not significantly different between group A and B (5.0 ml (20) vs 4.0 ml (19), p = 0.777). Both groups showed significant reduction in VAS scores in all five parameters (p ≤ 0.001). There were no complications attributed to endoscopy in either group. Pre-endoscopy maltodextrin beverage is as safe as clear water with improved patient's well-being in both groups.Clinical Trial Registration: NCT05106933.
Fulltext Empyema thoracis presented as giant back abscess

Abd Karim SH, Wan Zain WZ, Mohd Hashim MN, Zakaria AD, Hayati F, Ng CY

Radiol Case Rep, 2021 May;16(5):1061-1064.
PMID: 33680277 DOI: 10.1016/j.radcr.2021.02.030

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.
Fulltext Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression

Ahmad Zawawi SS, Mohd Azram NAS, Sulong S, Zakaria AD, Lee YY, Che Jalil NA, et al.

Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3099-3107.
PMID: 37774061 DOI: 10.31557/APJCP.2023.24.9.3099

BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-β1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.
Fulltext Contribution of Genetic Polymorphisms of Inflammation Response Genes on Sporadic Colorectal Cancer Predisposition Risk in Malaysian Patients - A Case Control Study

Ankathil R, Mustapha MA, Abdul Aziz AA, Mohd Shahpudin SN, Zakaria AD, Abu Hassan MR, et al.

Asian Pac J Cancer Prev, 2019 06 01;20(6):1621-1632.
PMID: 31244280 DOI: 10.31557/APJCP.2019.20.6.1621

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

Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al.

Sci Rep, 2021 02 03;11(1):2925.
PMID: 33536501 DOI: 10.1038/s41598-021-82465-0

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

Saizul Z, Siti-Azrin AH, Zakaria AD, Hassan A, Abdul Rahman WFW, Jalil NAC

Oman Med J, 2021 Jul;36(4):e284.
PMID: 34367685 DOI: 10.5001/omj.2021.83

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

Che Ghazali K, Mazian HA, Keat KC, Kai MWP, Md Hashim MN, Zakaria AD, et al.

J Surg Case Rep, 2019 Feb;2019(2):rjy345.
PMID: 30788087 DOI: 10.1093/jscr/rjy345

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.
Fulltext Trapped heart in heavily calcified pericardium

Zaimi MA, Mamat AZ, Ghazali MZ, Zakaria AD, Sahid NA, Hayati F

Oxf Med Case Reports, 2020 Oct;2020(10):omaa083.
PMID: 33133617 DOI: 10.1093/omcr/omaa083

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.
Diagnostic Value of Preoperative Haemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Predicting Tumour Budding in Colorectal Cancer

Hidrus A, Abdul Rahim SSS, Zakaria AD, Hayati F

J Coll Physicians Surg Pak, 2022 Nov;32(11):1514-1515.
PMID: 36377032 DOI: 10.29271/jcpsp.2022.11.1514

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

Sazali MF, Rahim SSSA, Hayati F, Mohd Daud MN, Avoi R, Omar A, et al.

J Public Health Res, 2021 Aug 04;11(1).
PMID: 34351098 DOI: 10.4081/jphr.2021.2377

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.
Traumatic Neck Injury: An Accidental Impalement by a Needlefish

Ali AA, Gurung R, Hayati F, Zakaria AD, Mohamad I, Ching FF

Wilderness Environ Med, 2021 Dec;32(4):517-521.
PMID: 34479771 DOI: 10.1016/j.wem.2021.07.006

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.
Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Perrone G, Giuffrida M, Abu-Zidan F, Kruger VF, Livrini M, Petracca GL, et al.

World J Emerg Surg, 2024 Apr 16;19(1):14.
PMID: 38627831 DOI: 10.1186/s13017-024-00543-w

BACKGROUND: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA.
METHODS: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up.
RESULTS: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 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 CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 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, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 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 CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.
Fulltext Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen

Abdul Aziz AA, Md Salleh MS, Yahya MM, Zakaria AD, Ankathil R

Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1319-1324.
PMID: 33906328 DOI: 10.31557/APJCP.2021.22.4.1319

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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