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  1. Abdul Ghaffar NA, Ismail MP, Nik Mahmood NM, Daud K, Abu Dzarr GA
    Maturitas, 2008 Jun 20;60(2):177-9.
    PMID: 18482807 DOI: 10.1016/j.maturitas.2008.03.013
    Uterine fibroid or leiomyoma is the commonest benign uterine tumour. Its occurrence in the postmenopausal age group is rare and if enlargement of the fibroid noted during this time, the diagnosis of leiomyosarcoma is provisional until proven otherwise. A case of a postmenopausal woman with a huge uterine fibroid associated with polycythaemia is presented whereby the mass was noted to increase in size within 2 years. The patient was otherwise well except for the growing uterine mass. She had venesection done to treat her polycythaemia and later underwent surgery for total abdominal hysterectomy and bilateral salpingoophoorectomy. The histopathology report confirmed leiomyoma of uterus with no evidence of sarcomatous changes. It was suggested that large uterine myoma may cause secondary polycythaemia by three postulated mechanisms, i.e. presence of hypoxia suggesting shunting within the tumour, second, the uterine fibroid was compressing the ureters resulting in inappropriate excessive production of erythropoietin by the kidneys, and third, the tumour itself may have been producing the erythropoietin.
  2. Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM
    Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
    PMID: 31030477
    Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
    common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
    degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
    therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
    factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
    Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
    obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
    ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
    using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
    ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
    positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
    the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
    with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
    [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
    type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
    The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
    prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).
  3. Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R
    Cancer Genet, 2017 02;211:18-25.
    PMID: 28279307 DOI: 10.1016/j.cancergen.2017.01.004
    This study aimed to investigate the association between FAS c.-671A>G polymorphism and cervical cancer risk in a case-control setting, followed by a meta-analysis of the published literatures. The case-control study involved genotyping of the polymorphism in 185 histopathologically confirmed cervical cancer patients and 209 cancer-free female controls utilizing PCR-RFLP technique, followed by logistic regression analyses. Meta-analysis was then conducted under homozygous, heterozygous, dominant, recessive and allele contrast models to combine data from 12 studies which consisted of 2798 cases and 3039 controls. Our case-control analysis revealed a significant association of the variant allele (G) and the homozygous variant genotype (GG) of the FAS polymorphism with an increased risk of cervical cancer. Subgroup analysis by ethnicity further confirmed the risk association in Malays (P  0.05). However, results of meta-analysis suggested a lack of association between the polymorphism and cervical cancer risk in all the five genetic models analyzed. In conclusion, while the FAS c.-671A>G polymorphism may serve as a biomarker for cervical cancer risk prediction among the Malays, there is a limited usability of the polymorphism as a cervical cancer risk biomarker in other populations.
  4. Zon EM, Afendi NR, Ismail MP, Ibrahim A, Che Hashim NAH
    Case Rep Womens Health, 2022 Oct;36:e00463.
    PMID: 36389633 DOI: 10.1016/j.crwh.2022.e00463
    Introduction: A retroperitoneal hematoma in obstetrics is very rare following spontaneous vaginal delivery. It requires a high index of suspicion, especially in a hemodynamically unstable patient with no active bleeding or external trauma postpartum, as early intervention is needed to prevent maternal morbidity and mortality. Conservative management may be an appropriate strategy in managing large hematomas even though surgical evacuation is classically recommended.

    Case: We report the case of a 39-year-old woman, para three, with a hematoma of the Retzius space after spontaneous uncomplicated vaginal delivery. The patient had sudden abdominal pain associated with urinary retention, two hours after delivery. She had a palpable mass at the anterior upper part of the vaginal wall, near the fornices, but no abnormality was detected at the labia majora, labia minora and lower part of the vagina. A transabdominal ultrasound scan revealed a mixed-echogenicity mass between the bladder and lower part of the uterus measuring 110 × 90 × 60 mm. The patient's hemoglobin level dropped from 12 g/dL to 10 g/dL. Given the patient's clinically stable state, she was managed conservatively with antibiotics, analgesics and one unit of packed red blood cells, and was discharged home day 5 postpartum.

    Conclusion: This case supports the conservative management of even large Retzius space hematomas for hemodynamically stable patients. A high index of suspicion and thorough evaluation are required when encountering a complaint of urinary retention and abdominal pain postpartum.

  5. Tan SC, Ismail MP, Duski DR, Othman NH, Bhavaraju VM, Ankathil R
    Cancer Invest, 2017 Mar 16;35(3):163-173.
    PMID: 28301252 DOI: 10.1080/07357907.2017.1278767
    This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.
  6. W Adnan WF, Nik Mahmood NMZ, Ismail MP, Mohamad Zon E, Othman MS, Kamaludin Z
    Cancer Treat Res Commun, 2022;33:100660.
    PMID: 36455511 DOI: 10.1016/j.ctarc.2022.100660
    BACKGROUND: Endometrial cancer in young women (less than 40-year-old) is associated with anovulatory menses, polycystic ovarian syndrome (PCOS) and subfertility. Endometrial cancer occurring in a miscarriage is rare. We highlight a case of endometrial cancer occurring during miscarriage of a non-viable pregnancy, its management and the outcome.

    CASE: A 32-year-old woman, Gravida 1 Para 0, was referred to our center at 7 weeks gestation in 2018 for uncontrolled diabetes mellitus diagnosed during investigation for subfertility. Her poor compliance with the treatment is consistent with an HbA1c of 8%. During the assessment, she was already complaining of lower abdominal pain. Ultrasound showed irregular IUGS with no fetal echo. She had a miscarriage soon; however, due to ultrasound evidence of thickened and irregular endometrium (17 mm) with mixed echogenicity, dilatation and curettage (D + C) were commenced. The first and second tissues were reported as the product of conception (POC) and well differentiated endometrioid adenocarcinoma, respectively. The first hysteroscopy showed foci area of polypoidal growth at the right posterior endometrium, obscuring the right ostium, with similar histology report. She was commenced on high-dose progestogen with hysteroscopy surveillance 6 months later, which showed disease regression. After two normal hysteroscopies and endometrial biopsies with continuous progestogen therapy for 12 months, cyclical progestogen for 12 months and follow-up for another 6 months, she had spontaneous conception and is currently pregnant at 16 weeks gestation.

    CONCLUSION: Endometrial cancer should be suspected in high-risk patients with first-trimester miscarriage. Individualized treatment with high dose progestogen and follow-up with the proper patient and partner counselling and education has high successful regressionand later on, pregnancy rate.

  7. Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R
    Biosci Rep, 2018 Apr 27;38(2).
    PMID: 29487170 DOI: 10.1042/BSR20171268
    Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population.
  8. Omar AA, Zon EM, Ismail MP, Mahdi M, Ibrahim A, Engku-Husna EI, et al.
    Med J Malaysia, 2023 Nov;78(6):711-716.
    PMID: 38031211
    INTRODUCTION: In gynaecology, laparoscopy is the choice of treatment for a lot of procedures as it is considered safe and effective. However, laparoscopic surgery requires skills that are different from those required for open surgery. In order to acquire the skills, a surgeon needs specific training. The aim of this study was to validate the AR Gynae endotrainer, a new mobile laparoscopic simulator, as a comparable box trainer for gynaecology laparoscopic training, comparing it with the well-established Karl Storz SZABO-BERCISACKIER laparoscopic trainer.

    MATERIALS AND METHODS: A randomised prospective crossover study was designed to compare the AR Gynae endotrainer versus Karl Storz SZABO-BERCI-SACKIER laparoscopic trainer as a tool for training gynaecology laparoscopic skills. Participants were assigned to perform two specially designed tasks used for laparoscopic training using both endotrainers. All subjects evaluated both simulators concerning their performance by the use of a questionnaire comparing: design, ports placement, visibility, ergonomics, triangulation of movement, fulcrum effect, depth perception, ambidexterity, resources for training, and resources for teaching. The overall score was defined as the median value obtained. The ability and time taken for participants to complete the tasks using both endotrainers were also compared. A total of 26 participants were enrolled in this study, including 13 Masters's students from the Department of Obstetrics & Gynaecology and 13 Masters's students from the Department of Surgery, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia.

    RESULTS: A better performance was observed with AR Gynae as compared to Karl Storz endotrainer in five out of ten items evaluated in the questionnaire. Additionally, the overall score of AR Gynae endotrainer (median of 3.98) was comparable to that of Karl Storz endotrainer (median of 3.91) with p=0.519. For the items design and resources for teaching, the evaluation for AR Gynae endotrainer was significantly higher with p-values of 0.003 and 0.032, respectively. All participants were able to complete both tasks using both endotrainers. The time taken to complete both tasks was comparable on both endotrainers. Also, the AR Gynae endotrainer was cheaper.

    CONCLUSIONS: The AR Gynae endotrainer was found to be a convenient and cost-effective laparoscopic simulator for gynaecology laparoscopic training and was comparable to the established Karl Storz SZABO-BERCI-SACKIER laparoscopic trainer.

  9. Abrar SS, Azmel Mohd Isa S, Mohd Hairon S, Yaacob NM, Ismail MP
    Cureus, 2024 Oct;16(10):e71359.
    PMID: 39534844 DOI: 10.7759/cureus.71359
    Cervical cancer is the fourth most common cancer among women worldwide, with particularly high incidence and mortality rates in low- and middle-income countries, with Asia reporting the highest number of cases in 2022. Despite this significant burden, the prognostic factors specific to Asian populations remain underexplored. This scoping review aimed to identify and evaluate prognostic factors associated with cervical cancer outcomes in Asia, focusing on clinical, socio-demographic, and treatment-related variables. The review followed the Arksey and O'Malley framework and included 44 studies published between 2013 and 2023. The majority of research was concentrated in East Asia, particularly in China, Japan, and South Korea. Key prognostic factors affecting overall survival and disease-free survival included tumor size, histology, age, lymphovascular invasion, and lymph node metastasis. Non-squamous cell carcinoma histology, especially adenocarcinoma, was consistently linked to poorer outcomes. Older age and medical comorbidities, such as anemia and diabetes, also negatively impacted survival. Treatment-related factors, though less frequently reported, demonstrated the significance of adjuvant therapy, chemotherapy, and treatment intensity in improving outcomes. This review underscores the complexity of cervical cancer prognosis in Asian populations and highlights the need for targeted research and region-specific interventions to address the rising incidence of cervical cancer. It also highlights the scarcity of research on cervical cancer prognostic factors in West, Central, and South Asian countries. Future research should aim to address the gaps in understanding treatment-related factors and explore the potential for region-specific interventions to improve outcomes in cervical cancer across Asia.
  10. Yahya MM, Ismail MP, Ramanathan S, Kadir MN, Azhar A, Ibrahim NBC, et al.
    Biomedicines, 2023 Feb 11;11(2).
    PMID: 36831061 DOI: 10.3390/biomedicines11020525
    Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient's clinical outcome.
  11. Yoon SY, Wong SW, Lim J, Ahmad S, Mariapun S, Padmanabhan H, et al.
    J Med Genet, 2022 Mar;59(3):220-229.
    PMID: 33526602 DOI: 10.1136/jmedgenet-2020-107416
    BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.

    METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.

    RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms.

    CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

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