Publications

BACKGROUND: Colorectal adenocarcinoma (CRC) remains a leading cause of cancer-related mortality worldwide, with variable patient outcomes despite treatment advances. Traditional prognostic methods based on clinicopathological variables alone do not fully capture the biological complexity of the disease. This study aims to develop a risk scoring system based on genes associated with tumour-infiltrating immune cells (TIIC-associated genes) to improve prognostic assessment in CRC.

METHODS: RNA-seq gene expression and clinicopathological data from The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA-CRC) database (647 tumour samples, 51 normal tissues) were analysed to identify differentially expressed TIIC-associated genes through comparison with the CIBERSORTx database. Univariate and multivariate Cox analyses were performed to screen for prognostic markers. A Gaussian mixture model was applied to cluster prognostic models and select the model with the most robust gene combination. The resulting risk scoring system was validated in an external cohort (GSE39582) and integrated with clinicopathological variables to develop a prognostic nomogram.

RESULTS: From 128 TIIC-associated genes, an optimal prognostic model comprising CCL8 and Tyrosinase (TYR) was identified. The risk score was calculated as 0.152 × Exp(CCL8)-0.516 × Exp(TYR). Kaplan-Meier analysis confirmed significant survival differences between high-risk and low-risk groups in both TCGA-CRC and GSE39582 (p < 0.05). Time-dependent receiver operating characteristic analysis showed area under the curve (AUC) values ranging from 0.605 to 0.696 for 1-, 3- and 5-year survival in TCGA-CRC and GSE39582. Multivariate Cox analysis identified tumour (T stage), node (N stage) and risk score as independent prognostic factors.

CONCLUSION: Our risk scoring system based on CCL8 and TYR effectively stratifies CRC patients into distinct prognostic groups and could guide treatment decisions, particularly when integrated with TNM staging in a nomogram.

Endometrial cancer (EC) treatment changed substantially with the introduction of molecular classification. There is a paucity of data regarding the added value of L1CAM in patients with p53 aberrant tumours. The present study aimed to analyse the prognostic value of L1CAM associated with p53 aberrant EC. Patients with EC treated between 2010 and 2016 were retrospectively evaluated. Patients included in this analysis must have reviewed high-grade histologies (endometrioid grade 3, serous, clear cell, carcinosarcoma, mixed and undiffrentiated). Samples were subjected to immunohistochemistry for L1CAM and p53. Recurrence-free survival (RFS) and overall survival (OS) were analysed by the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was performed for multivariable analysis. From 2010 to 2016, 464 patients met the inclusion criteria. Patients with p53 wild type and L1CAM negative (p53wt/L1CAMneg) corresponded to 13.6% (59 patients) of the population, p53 wild type and L1CAM positive (p53wt/L1CAMpos) to 11.7 % (51 patients), aberrant p53 and L1CAM negative (p53ab/L1CAMneg) to 32.9% (143 patients) and aberrant p53 with L1CAM positive (p53ab/L1CAMpos) to 41.8% (182 patients). In univariate and multivariate analysis, compared to patients with p53wt/L1CAMneg, the presence of p53wt/L1CAMpos, p53ab/L1CAMneg and p53ab/L1CAMpos was statistically associated with a worse RFS (HR 2.02; HR 2.20 and HR 2.99, respectively) and OS (HR 2.39; RH 2.31 and RH 2.94, respectively). In the present analysis of a high histological risk population, stages I-IV, we observed that the presence of p53ab/L1CAMpos was associated with a worse RFS and OS when comparing p53wt/L1CAMneg patients. Patients with L1CAMpos had the same worse prognosis as p53ab tumours.

BACKGROUND: Multiple myeloma (MM), a plasma cell malignancy, predominantly affects individuals aged 65-74 years. However, its occurrence in younger populations (<55 years) is rare, posing unique challenges. This study explores the clinical presentation, outcomes and treatment regimens for MM patients aged 30-55, aiming to unravel age-specific patterns.

METHODS: A retrospective chart review was conducted at Aga University Hospital, Karachi, focusing on MM patients aged 30-55 years. Data included patient demographics, clinical features, treatment modalities and outcomes. Statistical analysis employed STATA version 16.0, incorporating survival estimates, log-rank tests and Cox proportional survival regression models.

RESULTS: This study encompassed 68 confirmed MM patients, categorised by age groups: 30-40 years (13.23%), 41-50 years (44.11%) and 51-55 years (42.64%). Predominantly male (1.3:1 ratio), bone pains were prevalent among all groups, with 51-55 years exhibiting the highest pathological fracture rate. 30-40 years group showed higher renal impairment rates and lactate dehydrogenase levels. Velcade, thalidomide and dexamethasone were commonly used first-line regimens in the entire cohort in 41.17% of patients, closely followed by cyclophosphamide, bortezomib and dexamethasone in 29.41%. Partial response was predominant in the 30-40 years group, while other age groups showed varied responses. The younger patients demonstrated lower deep treatment response rates than their older counterparts. Progression-free survival was 37, 52 and 45 months orderly in each group, with a p-value of <0.001. The median overall survival (OS) for the entire group was 50.6 months (4.2 years), with OS rates of 77.8% (CI: 95%), 90.0% (CI: 95%) and 86.2% (CI: 95%), respectively, with a p-value of <0.001. Median OS in months was 45, 55.5 and 52, with a p-value of 0.08.

CONCLUSION: This single-center study sheds light on younger MM patients' unique challenges and treatment patterns. Despite the rarity of this age group's affliction, the findings underscore significant differences in clinical presentations, treatment responses and outcomes compared to the typical elderly MM population. The study highlights the importance of tailored approaches in managing MM across different age brackets, emphasising the need for further research to optimise therapeutic strategies and improve prognosis in this distinct patient cohort.

BACKGROUND: Adenoid cystic carcinoma of the breast (ACCB) is a rare histological subtype of breast cancer characterised by unique clinical features and management challenges. ACCB remains poorly understood, with limited data on its epidemiology, treatment outcomes and prognostic factors. This study aimed to elucidate the landscape of ACCB in a real-world context.

METHODS: A retrospective cohort study was conducted on patients diagnosed with ACCB in a Brazilian cancer center between January 2007 and October 2021. Clinical and pathological data were systematically collected from electronic medical records. Statistical analyses were performed to identify factors associated with prognosis and assess the impact of treatment interventions.

RESULTS: Twenty-one female patients with confirmed ACCB were included in the study. The median age at diagnosis was 55.2 years. Most patients had basaloid (38.1%) or classic (19.0%) histological subtypes. Adjuvant radiotherapy was associated with a trend towards better recurrence-free survival among patients with localised disease HR 0.21, CI 95% 0.04-1.06, p = 0.059). In the metastatic setting, systemic chemotherapy used for breast cancer demonstrated limited efficacy, with a median progression-free survival of 1.8 to 2.8 months. Despite the overall poor prognosis, two patients with low-volume metastatic disease had long-term survival following local therapy.

CONCLUSION: Given the rarity of ACCB and the absence of a standard management approach, this small study suggests a potential benefit of local therapies in adjuvant and metastatic settings while indicating the limited efficacy of systemic chemotherapy. Personalised treatment strategies tailored to ACCB are essential to optimising patient outcomes.

BACKGROUND: ehealth improves the health-related quality of life for cancer patients and their families by providing easier access to medical information, promoting self-management, and providing personalised care through digital platforms. However, there is still a dearth of comprehensive understanding of their influences in developing countries.

OBJECTIVES: To identify several ehealth interventions accessible to family caregivers of people with cancer in developing countries and to assess the impact of these interventions on their health-related quality of life.

METHODS: The review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. Health databases and search engines, including PubMed, Medline via Ovid, Embase via Ovid, and CINAHL via EBSCOhost, will be used. We will include quantitative or mixed method research evaluating e-health, with a particular emphasis on the health-related quality of life of family caregivers of cancer patients. Studies from developing countries, including peer-reviewed journals and grey literature, will be considered without regard to publication date.The study selection process involves screening titles and abstracts for relevance, then, doing a full-text assessment against the inclusion criteria. The Cochrane Risk of Bias tool for randomised controlled trials and ROBINS-I V2 for non-randomised studies will be employed to assess the quality of the included studies. The A Measurement Tool to Assess Systematic Reviews will assess the quality of this systematic review.

IMPLICATIONS: This review offers a thorough and impartial summary of current research on e-health tools and their impact on the health-related quality of life of family caregivers of cancer patients. It seeks to inform evidence-based decision-making across healthcare, policy development, and research design by identifying knowledge gaps, emphasising areas requiring further investigation, and steering future research.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024622302 https://www.crd.york.ac.uk/PROSPERO/view/CRD42024622302.

BACKGROUND: WHO's Global Initiative for Childhood Cancer (GICC) aims to increase global survival of childhood cancers to 60% by the year 2030 with a focus on six index cancers. However, there is no nationally representative epidemiologic data on these index cancers in Nigeria.

AIM: To describe the distribution, outcomes and determinants of GICC six-indexed cancer in Nigeria.

METHODOLOGY: A multi-centre ambi-directional cohort study of children was done in children <19 years diagnosed with any of acute lymphoblastic leukaemia (ALL), Wilms tumour (WT), retinoblastoma (RB), Hodgkin lymphoma (HL), Burkitt lymphoma (BL) or low-grade glioma (LGG). Seven centres in the six geopolitical zones of the country participated. A 2-year study with 18 months of retrospective data collection (January 2022-June 2023) and follow up of subjects was done for 6 months (July-December 2023).

RESULTS: A total number of 213 subjects were enrolled and ALL (n = 72;33.8%), WT (n = 57; 26.8%), RB (n = 52; 24.4%), BL (n = 17; 8.0%), HL (n = 13; 6.1%) and LGG (n = 2; 0.9%) accounted for the disease pattern. Median age at diagnosis was 5 years (51.6%). Mortality rate was 32.4% and treatment abandonment occurred in 37.6% of subjects. Treatment-related mortalities (TRMs) were 37.7% with infection and haemorrhage the commonest specific causes of TRM (36.1% and 42.5%). Only 7/95 (7%) of subjects with WT and RB stage III and IV benefited from RT. The most common reasons for non-RT were lack of funds (29%), lack of access to RT (54%) and lack of physicians' referral (11%). Only 10 (4.3%) of subjects were enrolled in a health insurance scheme. Independent risk factor for mortality was advanced disease stage (p = <0.001). Amongst the mortalities, 36% died within the first 3 months of diagnosis.

CONCLUSION: Treatment abandonment, mortality and TRM are high in Nigeria. To attain the GICC goal, there is a need to educate physician on treatment protocol, ensure availability of supportive care, health insurance, RT and tackle late presentation.

Synovial sarcoma is a rare and aggressive mesenchymal neoplasm characterised by the presence of the SS18-SSX fusion oncogene, resulting from the chromosomal translocation t(X;18)(p11.2;q11.2). Although these tumours typically arise in the extremities, they have also been documented in atypical locations such as the pericardium, underscoring their versatile and aggressive nature. This case involves a 46-year-old male who presented with a 2-month history of neck and precordial chest pain, ultimately diagnosed with a biphasic synovial sarcoma of the pericardium. Initial imaging studies, including magnetic resonance imaging and transthoracic echocardiogram, revealed a large encapsulated intrapericardial mass with hemorrhagic and thrombotic components, severe pericardial effusion and biventricular dysfunction. Histopathological examination confirmed the diagnosis, with immunohistochemistry findings positive for CKAE1/AE3, TLE-1, EMA, BCL-2 and CD99, along with a proliferation index of 40%. The chemotherapy regimen of ifosfamide, mesna and doxorubicin proved effective for this condition, leading to a significant reduction in tumour size and metabolic activity. However, due to disease recurrence and the presence of a KDM5A-positive marker, second-line therapy with trabectedin and pazopanib became necessary.

Cirrhosis is the fourteenth leading cause of death globally and significantly increases the risk of hepatocellular carcinoma (HCC). Polymorphisms in the vitamin D receptor (VDR) can influence inflammation, fibrosis progression and cancer susceptibility. We analysed the association of genetic polymorphisms of the VDR (VDR-rs2228570, VDR-rs731236 and VDR-rs7975232) in cirrhosis with or without HCC, considering clinical, biochemical profiles and survival. A total of 158 patients with cirrhosis, with or without HCC, were studied and distributed into Group 1 (G1 = 60): cirrhosis and HCC; Group 2 (G2 = 98): isolated cirrhosis and control group (G3 = 225): without liver disease. Genetic polymorphisms were analysed by real-time polymerase chain reaction; clinical and biochemical profiles were obtained from medical records. A significance level of α = 5% was adopted. The homozygous mutant for VDR-rs731236 and rs7975232 predominated in G1 compared to other groups (p < 0.05). For VDR-rs2228570, the homozygous mutant predominated in patients, while heterozygotes were found in controls (p > 0.05). A positive correlation between vitamin D and parathyroid hormone was observed in patients (R² = 0.3273). VDR-rs2228570 emerged as a protective factor for G2 (p = 0.0057) and was associated with increased survival, as was rs7975232. In conclusion, VDR-rs731236 and VDR-rs7975232 are associated with cirrhosis and HCC, with VDR-rs7975232 identified as independent predictors for isolated cirrhosis. VDR-rs2228570 confers protection and is associated with increased survival in cirrhosis, as well as a better clinical profile for both conditions in the Brazilian cohort. These findings highlight the potential clinical relevance of VDR polymorphisms as biomarkers for risk assessment and prognosis in cirrhosis and HCC.

BACKGROUND: Cervical cancer remains a significant public health issue, particularly in low-income countries. It is the fourth most common cancer among women globally, with an estimated 570,000 new cases and 311,000 deaths in 2018.

OBJECTIVE: This study aimed to examine the stages of cervical cancer at diagnosis and identify factors contributing to late-stage presentation among women in a tertiary care hospital in Nigeria.

METHODS: A retrospective study analysed data from women diagnosed with cervical cancer between 2017 and 2021. Demographic, reproductive and clinical data were extracted from medical records.

RESULTS: Of the 102 women who presented during the study period, only 57 (55.9%) had complete staging, clinical and demographic data; these complete cases were included to ensure data integrity. From this population, 73.7% were aged 50 years or older and 56.1% presented with late-stage disease. Additionally, anaemia (packed cell volume <30%) was present in 75.4% of women. Postcoital bleeding was reported in 35.1% of cases. Women with no formal education had higher odds of late-stage diagnosis odds ratios (OR: 4.40, 95% CI: 1.08-17.82). Postmenopausal women also had higher odds of late-stage diagnosis (OR: 4.46, 95% CI: 1.27-15.70).

CONCLUSION: A late-stage cervical cancer diagnosis is prevalent among women in Nigeria, particularly among those with lower educational levels and postmenopausal women. Targeted awareness programmes, expanded screening (including integration into well-woman/postmenopausal care) and improved healthcare infrastructure, including consistent documentation of screening history and human papillomavirus vaccination, are essential for reducing the burden of cervical cancer in this context.

BACKGROUND: Cancer remains a significant public health challenge, being the second leading cause of death in urban areas and the fourth in rural regions of India. The estimated 1.15 million new cancer cases in 2018 are projected to double by 2040. Despite the critical importance of early detection, cancer screening rates in rural India remain alarmingly low. This study investigates barriers to breast and cervical screening among women in remote villages of Karnataka using the Health Belief Model (HBM) as a theoretical framework.

METHODS: A community-based screening program for oral, breast and cervical cancer, was implemented in three taluks of Chikkaballapur district, Karnataka, from September to November 2021. Quantitative data from 4,974 screened women were complemented by qualitative interviews with 292 women who did not consent to screening, particularly for breast and cervical cancer. Interviews were guided by HBM constructs perceived susceptibility, severity, barriers, benefits, cues to action and self-efficacy and analysed thematically.

RESULTS: Out of the 4,974 women who participated in screening clinics, less than 10% consented to clinical breast examination and none to cervical screening. Major barriers to screening included socio-cultural factors (stigma, lack of awareness, peer pressure), economic constraints (work priorities and financial insecurity), psychological barriers (fear of outcomes and lack of healthcare trust) and physical challenges (accessibility and seasonal constraints). Fear of treatment outcomes and financial implications were prominent psychological deterrents. Mitigation strategies were noted to address these barriers, including awareness campaigns, flexible camp timings and local stakeholder engagement.

CONCLUSION: Addressing barriers to cervical and breast cancer screening requires a holistic, community-centred approach informed by theoretical models like HBM. Sustainable interventions must prioritise awareness, accessibility and affordability to bridge critical healthcare gaps and reduce the burden of cancer in rural India.