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Association of B-Lineage Lymphoblastic Leukaemia Gene Polymorphisms with Poor Prognostic Features

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4339-4349. doi: 10.31557/APJCP.2024.25.12.4339.

ABSTRACT

OBJECTIVE: Of this study was to analyse the correlation of gene polymorphisms with clinical and laboratory data of paediatric patients with B-lineage acute lymphoblastic leukaemia with prognostically unfavourable features.

METHODS: A study of 200 children with B-lineage acute lymphoblastic leukaemia (B-ALL) treated with polychemotherapy programmes was conducted. Analysis by sex revealed a statistically insignificant predominance of the group of boys over girls (54%). The mean age of the subjects was 9.3±0.2 years. Genotyping of polymorphic loci was performed using TaqMan method of single site-specific amplification and genotyping. The data of patients with initial prognostically unfavourable clinical and laboratory data in the form of initial leukocytosis from 50 to 99 thousand – 10 (5%), over 100 thousand – 16 (8%), initial CNS lesion in the form of neuroleukaemia – 5 (2.5%), initial splenomegaly more than 6 cm – 12 (6%); patients with poor response to therapy, having absolute number of blast cells in peripheral blood over 1,000 on day 8 of treatment according to the protocol (response to prednisolone prophase) – 13 (7%), with unsatisfactory response to treatment on Day 15 – 40 patients (20%) and on Day 33 – 4 children (2%); also patients who developed relapse of the disease – 17 (9%).

RESULTS: According to the findings, of all 24 gene variants, 13 variants (54%), namely, HLA – rs6457327, TNF – rs1800630 and rs2229094, GATA3 – rs3824662, TP53 – rs1042522, CASP9 – rs4661636, CASP8 – rs10505477, CEBPE – rs2239633; PIP4K2A – rs7088318, CASC8 – rs10505477, IRF4 – rs87207, CYP1A1 – rs4646903 and rs7089424 of ARID5B gene were found to be associated with B-ALL and unfavourable prognostic features.

CONCLUSIONS: The findings of this study revealed significant associations of polymorphic genetic variants, which may serve as a basis for the development of effective methods for predicting the risk of relapse development and the timeliness of intensification of B-ALL treatment. Prompt genetic counselling of children with identified unfavourable genotypes of the investigated gene polymorphisms will make it possible to predict the development of relapse, resistance and/or poor response to B-ALL treatment, and to propose an individual strategy for monitoring children’s health in the short and long term.

PMID:39733427 | DOI:10.31557/APJCP.2024.25.12.4339

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Efficacy of Omitting H2 Antagonists versus Famotidine in Taxane Hypersensitivity Reactions Prophylaxis: A Randomized, Prospective, Open-Label, Controlled Trial

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4333-4338. doi: 10.31557/APJCP.2024.25.12.4333.

ABSTRACT

OBJECTIVE: This study aims to evaluate the efficacy of premedication protocols in preventing immediate hypersensitivity reactions (HSRs) to taxane chemotherapy by comparing protocols that omit H2 antagonists with those that include famotidine.

METHODS: This was an open-label, single-center, randomized clinical trial. Randomization was 1:1 to two groups. The experimental arm omitted H2 antagonists from the premedication protocol, while the control arm included famotidine. The efficacy of the premedication protocol for preventing HSRs in the experimental group was compared with that of the control group using a multilevel regression analysis with a random intercept and random effect model.

RESULTS: Between September 2022 and December 2023, 150 patients enrolled. The group without H2 antagonists had 331 cycles, averaging 3.15 per patient. The famotidine group had 327 cycles, averaging 3.39 per patient. The total number of cycles was not significantly different (p = 0.951). There were six HSRs (1.81%) in the group without H2 antagonists and five (1.53%) in the famotidine group. The HSRs risk difference between groups was 0.28% (95% CI -0.02 to 0.02, p = 1.000). A multilevel regression analysis with a random intercept and effect model compared the efficacy of premedication protocols for preventing HSRs between the experimental and control groups. The risk ratio for HSRs in the group without H2 antagonists was 1.00, which was not statistically significant compared to the famotidine group (95% CI 0.98 to 1.04, p = 0.528).

CONCLUSION: The clinical trial demonstrated that omitting the H2 antagonists premedication protocol for taxane chemotherapy is as effective in preventing HSRs as using famotidine. These findings suggest that this protocol can be implemented in clinical practice.

PMID:39733426 | DOI:10.31557/APJCP.2024.25.12.4333

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Effect of Multi-component Exercise Program on Functional Performance in Breast Cancer Survivors

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4323-4331. doi: 10.31557/APJCP.2024.25.12.4323.

ABSTRACT

BACKGROUND: Breast surgery, radiation, chemotherapy and modified radical mastectomy (MRM) may cause long-term side effects such as decreased muscle strength, pulmonary function, cardio-respiratory fitness (CRF), altered body fat distribution and poor sleep quality. These short- and long-term repercussions have an enormous effect on physical functioning in this population. The goal of this research was to determine the effect of a multi-component exercise program on functional performance in breast cancer survivors.

METHODS: In this research, 132 women with breast cancer were selected based on specific inclusion criteria. Participants were separated in a pair of two groups: the control group, which participated in breast cancer support group therapy, and the experimental group, which engaged in a multi-component exercise program. Each group consisted of 66 participants. The study assessed functional performance using a 12-minute walk test and a sit-to-stand test. Over a year, the breast cancer support group and the multi-component fitness program were implemented. Pre- and post-assessments were used to determine the effectiveness of the multi-component workout program. Statistical evaluation was executed utilizing SPSS statistical software (version 26.0 for Windows; SPSS, Inc., Chicago, USA) to obtain the results.

RESULTS: The study findings indicate significant improvements in functional performance for the experimental group. Specifically, the sit-to-stand test showed extremely significant results (p-value of 0.0002), and the 12-minute walk test also demonstrated significance (p-value of 0.008). These positive outcomes highlight the effect of the multi-component exercise program in enhancing physical performance in breast cancer survivors.

CONCLUSION: The study revealed that both of the control group as well as the experimental group exhibited impaired functional performance in measures of outcome including 12-minute walk tests well as sit-to-stand test before the intervention. However, the multi-component exercise program had a notable positive impact on muscle performance among breast cancer survivors.

PMID:39733425 | DOI:10.31557/APJCP.2024.25.12.4323

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Environmental Management for Opisthorchis viverrini and Cholangiocarcinoma Prevention in a High-Risk Area of Thailand: The KALMeFS Model

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4305-4311. doi: 10.31557/APJCP.2024.25.12.4305.

ABSTRACT

OBJECTIVE: Despite the Ministry of Public Health’s initiative to involve local governments in waste management through the establishment of sewage treatment ponds aimed at disrupting the life cycle of Opisthorchis viverrini (OV), the majority of areas still lack adequate sewage treatment facilities. This action research sought to develop an environmental management model (EMM) to prevent OV and cholangiocarcinoma (CCA) in a high-risk region of Thailand.

METHODS: The study identified two primary target groups: a process development group comprising 20 participants and an evaluation group comprising 32 participants. Research tools involved structured interviews using questionnaires and focus group discussions. Quantitative data were analyzed using descriptive and inferential statistics, with a paired t-test employed for specific comparisons. Qualitative data were examined through content analysis.

RESULTS: The findings were categorized into three key aspects: (1) The contextual factors and challenges related to OV and CCA were analyzed using an epidemiologic triangle framework. (2) Model development: The Appreciation-Influence-Control (A-I-C) method facilitated several activities, including knowledge dissemination, raising awareness among local administrators, training environmental surveillance volunteer leaders (ESVL), developing public relations materials, conducting food waste management training, and constructing a sewage treatment system. (3) Model evaluation: Significant improvements (p<0.05) were observed in participants’ knowledge, attitudes, behaviors, and health beliefs regarding OV and CCA prevention. The outcome of these efforts led to the creation of a new model, termed the “KALMeFS Model,” which comprises K=Knowledge; A=Authority (raising awareness among administrators); L=Leader (establishing ESVLs); Me=Media development; F=Food waste management; and S=Sewage management.

CONCLUSION: The initial steps toward establishing an effective EMM for OV and CCA prevention involved comprehensive planning, knowledge dissemination, standard-setting, and implementation. Monitoring and evaluation are critical to ensuring the long-term success of CCA prevention efforts in Thailand.

PMID:39733423 | DOI:10.31557/APJCP.2024.25.12.4305

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Effect of Age, Hot Beverages and Tobacco Related Products on Buccal Epithelial Cells of Cigarette Smokers and non-Smokers in Ajman, UAE

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4293-4298. doi: 10.31557/APJCP.2024.25.12.4293.

ABSTRACT

OBJECTIVE: This study aimed to find out the effect of age, hot beverages and tobacco related products on buccal mucosa cells between cigarette smokers and non-smokers in Ajman, UAE.

METHODS: A total of 122 samples were collected, with demographic data including age, hot beverage consumption, cigarette smoking and other tobacco practice using pre-designed questionnaires. Buccal cells were collected, stained, and screened for micronuclei (MN) under a microscope and two evaluators independently assessed all the slides.

RESULTS: Among the 122 participants, 61.5% were aged ≤35 years, and 38.5% were aged >35 years. All non-smokers had MN values <10, while 87% of smokers had MN values >10 (p<0.001), with a trend of dose-dependent relationship between cigarette consumption and MN frequency. Similar patterns were observed in individuals using other forms of tobacco, with 97.4% exhibiting MN values >10 (p<0.001). Hot beverage consumption ≥7 cups/day was associated with 87% of subjects having MN values >10, highlighting the pattern of alternative forms of tobacco and high consumption of hot beverages association with elevated MN occurrence. Significant associations were found between MN and variables, except for age.

CONCLUSION: The findings underscore the significance of tobacco and hot beverage consumption in MN occurrence, emphasizing the need to address these behaviors to mitigate genotoxicity and associated health risks. Despite age showing no significant correlation with MN frequency within the studied age range, aging combined with cigarette smoking amplifies genetic damage.<br />.

PMID:39733421 | DOI:10.31557/APJCP.2024.25.12.4293

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Effect of Anaesthesia Technique on anti-tumor Immunity through TGF-β levels in Adult Patients Undergoing Surgery for Oral Cancer

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4257-4264. doi: 10.31557/APJCP.2024.25.12.4257.

ABSTRACT

BACKGROUND: There is a paucity of literature regarding the effect of anesthetic techniques on anti-tumor immunity, especially in Oral cavity Malignancies. We designed a study to evaluate the effect of 3 anesthetic techniques – Opioid, Lignocaine infusion and Dexmeditomedine infusion-based on anti-tumor immunity, using TGF-β, T-helper cell profile and inflammatory markers such as IL-6 and IL-10.

METHODS: A pilot prospective randomized trial was conducted in 90 patients undergoing surgery for Oral cavity malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of the American Society of Anaesthesiologists (ASA) physical status I-III fulfilling the inclusion criteria were randomized to either group A (Opioid general anesthesia), group B (lignocaine infusion-based general anesthesia), or group C (Dexmedetomidine infusion-based general anesthesia). Preoperative (morning of surgery) and postoperative (24 hours after surgery) blood samples were obtained. Statistical analysis was done, and the results were analyzed.

RESULTS: Demographic profile and pre-operative parameters were comparable between both groups. We did not find any statistically significant difference in the Post-operative levels of TGF-β, neutrophil-lymphocyte ratio (NLR), Monocyte Lymphocyte Ratio (MLR), platelet lymphocyte ratio (PLR), IL-6, IL-10, and T-helper cell profile( IFN-γ, IL-17A, and IL-4 as surrogate markers) among the three study groups. However, it was noted that the overall Opioid consumption was markedly reduced in Group C without any major adverse effects being noted.

PMID:39733417 | DOI:10.31557/APJCP.2024.25.12.4257

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Factors Associated with Hepatocellular Carcinoma among Patients Receiving Treatment at the National Cancer Institute, Thailand: A Case-Control Study

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4169-4174. doi: 10.31557/APJCP.2024.25.12.4169.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major public health concern in Thailand, ranking as the leading cause of cancer-related mortality in Thai people. This study aimed to identify various risk factors for HCC among patients treated at the National Cancer Institute (NCI) in Thailand.

METHODS: The retrospective case-control study was conducted using secondary data sources from the Liver Cancer Prevention and Control Research project which was carried out at NCI from 2008 to 2010. A total of 200 cases diagnosed with HCC and 300 healthy controls were included in this study. Univariate analysis and multivariate logistic regression models were used to identify independent risk factors associated with HCC development. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to quantify the strength and significance of these associations.

RESULTS: Our analysis showed that the mean ages of cases and controls were 52.2±7.7 years and 53.5±8.2 years respectively. After adjustment for gender, marital status, education, and income, the multivariable logistic regression analysis revealed a statistically significant association between HCC and several other factors. These included hepatitis B virus infection (OR 5.7, 95% CI 2.8-11.6), hepatitis C virus infection (OR 8.2, 95% CI 1.1-60.1) liver cirrhosis (OR 15.7, 95% CI 3.9-63.4), diabetes (OR 3.5, 95% CI 1.5-8.2), alcohol consumption (OR 3.2, 95% CI 1.7-5.9), and smoking status (OR 2.5, 95% CI 1.2-4.9).

CONCLUSIONS: Our findings contribute to the existing knowledge regarding risk factors for HCC among Thai people, particularly highlighting the emerging evidence that associates diabetes with HCC. This study provided baseline information for improving knowledge focused on preventing HCC and avoiding associated risk factors.

PMID:39733406 | DOI:10.31557/APJCP.2024.25.12.4169

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Relationship between Quality Practice Metrics and Treatment Outcomes in Hospitalized Cirrhotic Patients

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4153-4159. doi: 10.31557/APJCP.2024.25.12.4153.

ABSTRACT

BACKGROUND/AIMS: Variations in cirrhosis management practices and care quality affect patient prognoses and outcomes. We aimed to evaluate the number of successful cirrhosis care processes and the relationship between the quality statement implementation and clinical outcomes in patients with cirrhosis.

METHODS: This retrospective cohort study included hospitalized patients with cirrhosis. Eighteen process-based methods were independently assessed. Measurement indices for each participant were selected per cirrhosis severity. Service quality was determined using standard settings for each process-based gap scale. The optimal care group comprised participants who adhered to all instruction quality indices. Kaplan-Meier survival analysis assessed the 90-day readmission and mortality rates relating to the optimal quality care.

RESULTS: Of the 205 patients (73.2% male; mean age, 62.7±11.8 years), the median Model for End-stage Liver Disease score was 15.35 (9.37-21.37), and the majority were Child-Pugh B/C. Previously set performance gaps were observed for 13/18 quality processes, and 5/13 clinical processes attained the final goal. Paracentesis in ascites patients, antibiotic administration within 12 hours of spontaneous bacterial peritonitis diagnosis, and precipitating factors identification with lactulose therapy were the top three quality index (QI) accomplishments. Out of 205 patients, 84 attained optimal care. Concerning optimal care, although the readmission rate remained same, patients with decompensated Child-Pugh C who received excellent complete QI care had significantly increased both 1-month (100% vs. 43.5%; p=0.022) and 3-month (100% vs. 26.1%; p=0.022) survival in comparison to those receiving incomplete QI care.

CONCLUSION: Using quality metrics for the appropriate stage of individual cirrhosis treatment is advocated as best practice. Adherence to standard practices improves clinical outcomes.

PMID:39733404 | DOI:10.31557/APJCP.2024.25.12.4153

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Mutation Spectrum Analysis of BRCA1/2 Genes for Hereditary Breast and Ovarian Cancer in the Indian Population

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4145-4151. doi: 10.31557/APJCP.2024.25.12.4145.

ABSTRACT

OBJECTIVE: The objective of this study was to determine the prevalence and spectrum of genetic mutations linked to inherited breast and ovary cancer (HBOC) in the Indian population, and to evaluate the correlation of BRCA mutation types, frequency, and incidence with age, gender, and personal and family history.

METHODS: A retrospective cohort of 500 Indian HBOC patients, meeting NCCN criteria who underwent BRCA1/2 testing from 2017 to 2023 were shortlisted for this study. The anonymized data was retrieved from medical records. Genetic analysis was conducted using Next Generation Sequencing (NGS) on the Thermo Ion GeneStudio™ S5 System, with positive mutations confirmed via Sanger sequencing. Peripheral blood samples were processed for DNA extraction, library preparation, and variant classification following ACMG guidelines.

RESULTS: Out of the 500 patients, 119 (23.8%) were positive for BRCA mutations, and 381 (76.2%) were negative. The prevalence of BRCA pathogenesis, likely pathogenicity, and variants of uncertain significance (VUSs) were 14.8%, 1.6%, and 7.4%, respectively. A total of 128 mutations were detected in the positive BRCA1/2 patients. A statistically significant correlation was found between BRCA mutations with the patient and family history. A total of 38.8% of the patients with mutations had a family history of BC, OC or BC/OC, while 7.6% had other cancers. BRCA mutations were predominant (26.2%) in the age group of 46-65 Y. Among the 128 mutations, 59.3% (76/128) and 40.6% (52/12) of the patients had mutations in BRCA1 and BRCA2, respectively. Missense mutations were the most common in both the BRCA1 (30.26%) and BRCA2 (55.77%) genes, followed by frameshift (22.3%) and nonsense (17.3%) mutations in BRCA1 and BRCA2, respectively.

CONCLUSION: BRCA positivity was detected in 23.8% of the patients. A statistically significant association was shown between BRCA mutations and patient and family history.

PMID:39733403 | DOI:10.31557/APJCP.2024.25.12.4145

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P53 and Ki67 Biomarkers are Predictors for Malignant Transformation in Oral Submucous Fibrosis: A Prospective Study

Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4129-4136. doi: 10.31557/APJCP.2024.25.12.4129.

ABSTRACT

OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially malignant disorder (PMD) characterized by a high rate of malignant transformation (MT). OSMF exhibits atrophic epithelium yet has a high proliferation rate. Both p53 and Ki67 are nuclear proteins associated with cell proliferation, detectable in the early stages of oral cancer (OC). This study aimed to analyze the efficacy of p53 and Ki67 immuno-expression as tools for predicting malignant transformation in OSMF cases. The objective was to correlate the expression of p53 and Ki67 with demographic and chewing habits data.

MATERIALS AND METHODS: The study group consisted of 60 histopathologically diagnosed cases of OSMF, 60 cases of OC as positive controls, and 60 cases of NOM as negative controls. Immunohistochemistry was performed on neutral-buffered formalin-fixed, paraffin-embedded tissue sections of 3 μm thickness, using ready-to-use anti-human p53 protein (clone DO-7) and monoclonal antibody for Ki67 antigen (clone MIB-1). Statistical analysis was conducted using SPSS software version 21, employing the chi-square test (p < 0.05).

RESULTS: The expression of p53 and Ki67 was significantly higher in OSMF samples compared to NOM samples, but lower than in OC samples. When the expression levels of both p53 and Ki67 were correlated with demographic and chewing habits data, the results were statistically significant.

CONCLUSION: The overexpression of p53 and Ki67 may contribute to the progression of MT in OSM. Early detection of these biomarkers is crucial for preventing MT, which also helps reduce the morbidity and mortality of OC. Therefore, both p53 and Ki67 can serve as predictive biomarkers for the early detection of MT in high-risk OSMF patients.

PMID:39733401 | DOI:10.31557/APJCP.2024.25.12.4129