OAR@UM Collection:

The role of biochemical markers and genetic susceptibility in the pathogenesis of hormone dependent malignancies

2023-03-13T07:07:43Z

Title: The role of biochemical markers and genetic susceptibility in the pathogenesis of hormone dependent malignancies Abstract: Introduction: Multiple studies have associated the global increase of postmenopausal breast and endometrial cancer with the worldwide increase in obesity and the metabolic syndrome. The Maltese population has also been repeatedly shown to have markedly increased obesity, metabolic syndrome and insulin resistance, with increasing trends of breast and endometrial cancers. Aims: To evaluate which markers - metabolic/hormonal and genetic markers related to the metabolic syndrome – are associated with increased risk of breast and/or endometrial cancer. Also, it aims to compare the performance of polygenic risk scores relative to anthropometric/clinical predictors in classifying cancer from control patients. Method: A random sample of three study populations was recruited: Study Group 1- Patients with a history of endometrial carcinoma; Study Group 2 - Patients with a history of breast carcinoma; and Study Group 3: A control group including women with histologically confirmed absence of endometrial carcinoma (after hysterectomy) and no history of breast carcinoma. All the patients recruited were postmenopausal patients of Maltese ethnicity. Each subject was interviewed and anthropometric data measured. Blood was collected for biochemical and hormonal tests. The risk factors were associated with breast/endometrial cancer risk and logistic regression was done. DNA was extracted from whole blood and genetic profiling by LP-WGS was then carried out. Association of genetic risk scores of single nucleotide polymorphisms known to be association with diabetes mellitus type II and insulin resistance were determined by logistic regression. Results: 300 patients have been recruited - 132 patients were diagnosed with breast cancer, 90 patients with endometrial cancer (four patients had both endometrial and breast cancer) and 82 patients controls. The study observed a positive association between early menarche, nulliparity and high BMI with both breast (p=0.02, p=0.049, and p=0.04 respectively] and endometrial cancer risk (p=0.01, p=0.017, p<0.01) respectively. Family history of breast cancer and high SHBG level were also found to be associated with increased breast cancer risk (p=0.009 and p=0.02 respectively) while a positive association between history of hypertension (p<0.01), diabetes mellitus type 2 (p<0.01), presence of the metabolic syndrome (p<0.01), family history of hypertension (p=0.007), high serum triglycerides (p<0.01), HbA1C (p<0.01), HOMA-IR (p=0.01) were found with endometrial cancer. History of breastfeeding was observed to be negatively associated with both breast (p<0.01) and endometrial cancer risk (p<0.01). Serum FSH and LH levels were also found to be negatively associated with breast cancer (p<0.01 and p<0.01 respectively) while serum SHBG and progesterone showed a negative association with endometrial cancer (p=0.01 and p=0.01 respectively). The logistic regression models showed that that BMI was the best predictor of breast and endometrial cancers - for every 1 kg/m2 increase in BMI, the odds of having breast cancer increased by 3.9% (OR=1.039) while the odds of having endometrial cancer increased by 8.4% (OR=1084). Genetic profiling showed that a greater number of alleles from genetic risk scores with loci for diabetes mellitus type 2 and insulin resistance were significantly present in the breast and endometrial cancer cohorts. After adjustment for age, fasting insulin, fasting glucose, WHR and serum triglycerides level, quintile 5 of GRS 1 was found to have an OR for cancer risk (breast/endometrial) of 21.738 (p<0.01). Conclusion: This study gave better understanding on the risk significance of various factors related to breast and endometrial carcinogenesis in the Maltese population. By determining risk factors, women can be risk-stratified and individualised intervention/s can be implemented according to their risk for developing breast/endometrial cancer. Description: Ph.D.(Melit.)

The influence of applying the NICE guideline on CTG interpretation and classification during labour and on resultant clinical management in Malta

2023-03-10T05:56:20Z

Title: The influence of applying the NICE guideline on CTG interpretation and classification during labour and on resultant clinical management in Malta Abstract: Background: Despite the existence of clinical guidelines to aid in cardiotocography (CTG) interpretation during labour, variation remains amongst observers. This study aimed to assess the influence of applying the NICE (2017) guideline on CTG interpretation and classification during the active first stage of labour and resultant clinical management at the public hospital in Malta. Further objectives include to note interobserver agreement within and between groups of obstetricians, obstetric trainees and midwives when interpreting and classifying CTGs and to examine the type of clinical management decisions taken, while following the NICE (2017) guideline. Methods: A total of 17 intrapartum CTGs were obtained retrospectively from inpatient records. Participants were recruited from the entire staff population (n=90) on voluntary basis, aiming to obtain a stratified sample. A survey containing the CTGs and questions based on the NICE guideline, regarding CTG interpretation, classification and clinical management was disseminated to participants. Responses were analysed between obstetricians, trainees and midwives using Fleiss’ Kappa statistic for interobserver agreement on CTG interpretation within and between groups while percentage frequencies were applied to analyse type of classification and management responses. Statistical software IBM® SPSS® version 28 and Minitab® version 21 were used. Results: A mixed sample of 25 participants was obtained, resulting in a response rate of 33.8%. High levels of agreement were achieved when interpreting decelerations, while poor agreement was observed for interpreting baseline FHR, accelerations and variability. Normal CTG classifications achieved the highest interobserver agreement amongst all groups; with midwives achieving highest kappa values but weak agreement (k=0.516; CI 95% 0.413-0.620; P 0.000). Variation was noted for clinical management options chosen for each trace. Participants chose to ‘expedite birth’ for 53% (n=17) of CTGs, even in normal traces. Conclusion: Despite following a standard guideline which is meant to aid in CTG interpretation and classification, interobserver agreement is still overall poor and variation remains a challenge. Future studies with larger samples are recommended as well as maintain regular CTG interpretation workshops in clinical practice. Description: M.Sc.(Melit.)

A retrospective study of emergency caesarean sections performed for prolonged labour in primiparous singleton pregnancies delivered in the Maltese islands

2023-03-01T12:25:33Z

Title: A retrospective study of emergency caesarean sections performed for prolonged labour in primiparous singleton pregnancies delivered in the Maltese islands Abstract: Evidence suggests that changing institutional practice to provide more time before caesarean birth for slow progress reduces the rate of caesarean delivery in nulliparous women (A. Caughey et al., 2014). Morton et al. carried out a retrospective observational study of all caesarean deliveries in Sydney, Australia between 1989 and 2016. The rates and indications for emergency and elective caesarean deliveries were the primary outcome measures. Their sample size was 147722 births, with caesarean sections accounting for 25.3% of the deliveries. They observed a substantial increase in the rate of caesarean delivery during their study period. Emergency CS rose from 8.7% to 11.4%, whereas elective CS rates nearly doubled from 10% to 19%. Emergency caesarean delivery for slow progress increased from 3.4% to 5.5% of all births. Next most common indication for this intervention was suspected intrapartum fetal compromise (Morton et al., 2020). The authors concluded that the observed outcomes are due to a rise in the number of procedures conducted for poor labour progress, breech presentation, or repeat caesarean section. The trend of increasing emergency procedures performed for poor labour progress warrants additional investigation. Studies of recent data from the Consortium on Safe Labour in the United States (A. B. Caughey et al., 2014) recommend that the active first stage of labour should be redefined to 6 cm of cervical dilatation (Cohen and Friedman, 2015). This is based on the observation that most consistent and rapid progress could be witnessed beyond this threshold. At less than 6 cm dilation, half of all caesarean births for slow progress were performed (A. B. Caughey et al., 2014). Other researchers have discovered that a substantial proportion of caesarean sections for poor progress are initiated before this point, implying that some of these operations are unnecessary (Zhang, Troendle, et al., 2010; C. Riddell et al., 2017). An emergency caesarean section is defined as an operative delivery performed despite the plan for a vaginal delivery from the onset of labour, or for an acute emergency such as placental abruption. The two categories of emergency caesarean indications are slow progress and others like a suspected intrapartum fetal compromise. First and second-stage protraction and arrest disorders, including failed instrumental delivery and unsuccessful induction of labour may result in poor progress. Fetal distress, late deceleration on CTG (cardiotocograph) and fetal bradycardia are indicators of fetal compromise. All other caesarean deliveries are categorised as planned or elective and are decided by an obstetrician during antenatal visits. Planned indications include macrosomia, big baby, CPD (cephalo-pelvic disproportion), high head, short stature, LGA (large for gestational age), malpresentation including breech and compound presentations, malposition, placental problems such as placenta previa, AMA (advanced maternal age), maternal request, STD (sexually transmitted disease), other maternal comorbidities and fetal anomalies. Description: M.Sc.(Melit.)