The immune system plays an important role in protecting the body against malignancy. During cancer immunoediting, the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel molecules. However, the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming cells. Human Leukocyte Antigen G (HLA-G) is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against them. HLA-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound protein. HLA-G locus is highly polymorphic in the non-coding 3' untranslated region (UTR) and in the 5' upstream regulatory region (5' URR). HLA-G expression is controlled by polymorphisms located in these regions, and several association studies between these polymorphic sites and disease predisposition, response to therapy, and/or HLA-G protein expression have been reported. Various polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer biology. This review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer development. We highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis, prognosis and immunotherapy in the currently understudied African population.
Abstract Background Pediatric sarcomas represent an important group of childhood tumors who require treatment at Muhimbili National Hospital (MNH), the largest pediatric oncology center in Tanzania. Treatment is often adapted from established childhood protocols validated in clinical trials from the United States and United Kingdom. There are no studies describing the outcomes of treatment in Tanzania to understand similarities and disparities with other countries. The objective of this study was to describe the treatment outcomes including the overall survival for children seen at MNH. Methods Data on treatment outcome was collected on all children seen at MNH pediatric oncology unit between 2011 and 2016 with a confirmed histological diagnosis of either bone or soft tissue sarcoma. Results A total of 135 cases were analyzed; 89 (66%) were Soft tissue sarcoma (STS) and 46 (34%) were bone sarcomas. In the STS group, 37 (41.6%) achieved a complete response, 12 (13.5%) achieved a partial response and 40 (44.9%) had no response. Factors found to be significantly associated with a higher complete response rate included early stage disease (stage I or II), embryonal histology, tumor in favorable sites and tumor size of <5cm for STS and <8cm for the bone sarcomas. There was a trend for better 2-year overall survival for STS in early stage disease (74.5%) compared to late stage disease (20.6%), p<0.001. A similar trend was noted for the bone sarcomas; 91.7% versus 25.3% for early stage and late stage disease respectively, p=0.001. Conclusions This report is the first study documenting the treatment outcome for pediatric sarcomas seen in Tanzania. Disease stage is strongly related to treatment outcome with later stages of the disease having an overall poor prognosis.
Background: Colorectal carcinoma usually arises from an adenomatous polyp and observational studies suggest that the adenoma-to-carcinoma sequence takes approximately 10 to 15 years. Risk factors are adoption of westernized diets, obesity, cigarette smoking, and alcohol and reduced physical activity. Clinical Presentations are blood per rectum, abdominal pain, Anemia, change in bowel habits and bowel obstructive symptoms. The treatment of colorectal cancer is a dependent stage which includes chemotherapy, radiotherapy, surgery or both. Objective: This study aims at describing the clinical pathological characteristics of colorectal carcinoma and factors influencing survival among patients treated at Ocean Road Cancer Institute. Methods: This was a cross sectional study that involved histological confirmed colorectal carcinoma treated at Ocean Road Cancer Institute from 2010-2015. Results: Among 100 files extracted, 63% were males and 37% females. 21% were below 40 years of age. Left-sided tumor accounted for 46%. Abdominal pain, rectal bleeding and constipation were 72%, 68% and 55% respectively. Moderately differentiated adenocarcinoma accounted for 80%. Patients presented at stage III and IV were 37% and 56% respectively. Colostomy was the most surgical procedures performed. Folinic acid, Fluorouracil and Oxaliplatin were the most common chemotherapies used. Median overall survival was estimated to be 9.4 months. Conclusion: A significant proportion of patients in this study population are young. Survival from colorectal cancer is poor owing largely to the late presentation seen in this study group.
This study assessed the efficiency of offline setup correction protocol and the use of a thermoplastic mask for head and neck cancer (HNC) patients treated with three-dimensional conformal radiotherapy at Ocean Road Cancer Institute. A prospective study was conducted from April to August 2021 to verify 62 patients’ treatment setup using an offline setup correction protocol while immobilized with a thermoplastic mask. Megavoltage images were matched with digitally reconstructed radiographs obtained during CT simulation to determine the gross set-up deviations. Box plots were used to show the deviations on three consecutive days of the first week and a successive weekly set-up verification in lateral, longitudinal, and vertical directions. The associations between thermoplastic mask types and weekly deviations were analyzed using repeated test ANOVA. A p-value ˂ 0.05 was considered statistically significant. The observed deviations after the use of correction protocol were lower in all three translational directions. There was no statistical significance between types of thermoplastic mask and setup deviations in lateral (p < 0.65), longitudinal (p = 0.19), and vertical (p = 0.12) directions. The offline correction protocol can be used in settings with limited resources and high workloads of patients. Both types of thermoplastic masks are effective in immobilizing HNC patients.
Tracheostomy is a lifesaving, essential procedure performed for airway obstruction in the case of head and neck cancers, prolonged ventilator use, and for long-term pulmonary care. While successful quality improvement interventions in high-income countries such as through the Global Tracheostomy Collaborative significantly reduced length of hospital stay and decreased levels of anxiety among patients, limited literature exists regarding tracheostomy care and practices in low and middle-income countries (LMIC), where most of the world resides. Given limited literature, this scoping review aims to summarize published tracheostomy studies in LMICs and highlight areas in need of quality improvement and clinical research efforts. Based on the PRISMA guidelines, a scoping review of the literature was performed through MEDLINE/PubMed and Embase using terms related to tracheostomy, educational and quality improvement interventions, and LMICs. Publications from 2000-2022 in English were included. Eighteen publications representing 10 countries were included in the final analysis. Seven studies described baseline needs assessments, 3 development of training programs for caregivers, 6 trialed home-based or hospital-based interventions, and finally 2 articles discussed development of standardized protocols. Overall, studies highlighted the unique challenges to tracheostomy care in LMICs including language, literacy barriers, resource availability (running water and electricity in patient homes), and health system access (financial costs of travel and follow-up). There is currently limited published literature on tracheostomy quality improvement and care in LMICs. Opportunities to improve quality of care include increased efforts to measure complications and outcomes, implementing evidence-based interventions tailored to LMIC settings, and using an implementation science framework to study tracheostomy care in LMICs.
Background: In Tanzania Wilms tumor (WT) ranks second among the most frequently diagnosed childhood cancer. Due to late presentation an intensified treatment protocol was established aiming for tumor reduction before surgery for achieving better surgical outcomes. We used two indicators for measuring the protocol concordance. First indicator was assessing the number of patients that received radiotherapy and second was number of patients treated with the high-risk regimen as per the protocol indications.Methodology: This was a cross sectional study. Data was collected using a retrospective chart review of all children with WT at Muhimbili National Hospital Pediatric Oncology Unit for a period between April 2016 to May 2017 who were treated using the intensified treatment protocol (combination of two WT protocols with neoadjuvant as per SIOP-PODC and adjuvant as per modified SIOP International). Analysis was conducted using excel sheet and SPSS v20.Results: A total of 74 children were eligible. The median age was 3 years ranging from 6 months to 17 years with small female predisposition of 57% (n=42). On clinical presentation all patients presented with history of abdominal swelling. In terms of clinical stage; 45% (n= 33) and 43% (n= 32) presented with stage 4 and 3 disease, respectively. Radiotherapy treatment was administered to 30% (n=22). As per protocol stage III and IV disease require radiotherapy thus only 34% of eligible candidates received radiotherapy. On histology report; 34% (n = 25) reports were never found and 66% (n=49) were available. High-risk cases were 27% (n = 20). We noted high-risk regimen was given to 12% (n=9) of study participants; thus only 45% of eligible candidates received high-risk regimen. All patient had intention to treat on admission with noted 19% (n = 14) default rate.Conclusion: Measuring concordance with guidelines allows for identification of best practices, which in turn inform on quality improvements. This snapshot identified opportunities for improvement in protocol uptake in our unit.
Key words: Wilms Tumor, low income country, pediatric malignancy.
The germline BRCA1 c.68_69delAG (185delAG) and c.5266dupC (5382insC) mutations are associated with hormone receptor-negative breast cancer (BC). Limited studies have examined their contribution to alarming BC incidence in Sub Saharan Africa (SSA). Our study aimed to examine the contribution of germline BRCA1 c.68_69delAG and c.5266dupC mutations to BC incidence among hormone receptor-negative BC patients admitted to Ocean Road Cancer Institute in Tanzania. Face-to-face interviews were conducted to capture socio-demographic characteristics, anthropometric measurements, family history of cancer and reproductive information from each patient. Their histopathological data were extracted from the hospital medical records. The germline BRCA1 founder mutations were analyzed on blood samples using Sanger sequencing technology. The patients mean age at diagnosis was 47.05 ± 12.82 years. A family history of cancer was observed in 13.6% of patients. The germline BRCA1 c.68_69delAG and c.5266dupC mutations were not detected in the study group. Our findings indicate that the germline BRCA1 c.68_69delAG and c.5266dupC mutations do not contribute to BC manifestation in hormone receptor-negative BC patients in Tanzania. Thus, screening BC patients for these mutations has no clinical relevance. Our data further suggest that the c.68_69delAG and the c.5266dupC mutations should not be considered when developing genetic testing guidelines in Tanzania.
Keywords: Breast cancer, germline BRCA1 mutation, c.68_69delAG (185delAG), c.5266dupC (5382insC), Tanzania
Abstract Background Recent epidemiological studies suggest that reproductive factors are associated with breast cancer (BC) molecular subtypes. However, these associations have not been thoroughly studied in the African populations. The present study aimed to investigate the prevalence of BC molecular subtypes and assess their association with reproductive factors in Tanzanian BC patients. Methods This hospital-based case-only cross-sectional study consisted of 263 histologically confirmed BC patients in Tanzania. Clinico-pathological data, socio-demographic characteristics, anthropometric measurements, and reproductive risk factors were examined using the Chi-square test and one-way ANOVA. The association among reproductive factors and BC molecular subtypes was analyzed using multinomial logistic regression. The heterogeneity of the associations was assessed using the Wald test. Results We found evident subtype heterogeneity for reproductive factors. We observed that post-menopausal status was more prevalent in luminal-A subtype, while compared to luminal-A subtype, luminal-B and HER-2 enriched subtypes were less likely to be found in post-menopausal women (OR: 0.21, 95%CI 0.10–0.41, p = 0.001; OR: 0.39, 95%CI 0.17–0.89, p = 0.026, respectively). Also, the luminal-B subtype was more likely to be diagnosed in patients aged ≤ 40 years than the luminal-A subtype (OR: 2.80, 95%CI 1.46–5.32, p = 0.002). Women who had their first full-term pregnancy at < 30 years were more likely to be of luminal-B (OR: 2.71, 95%CI 1.18–4.17, p = 0.018), and triple-negative (OR: 2.28, 95%CI 1.02–4.07, p = 0.044) subtypes relative to luminal-A subtype. Furthermore, we observed that breastfeeding might have reduced odds of developing luminal-A, luminal-B and triple-negative subtypes. Women who never breastfed were more likely to be diagnosed with luminal-B and triple-negative subtypes when compared to luminal-A subtype (OR: 0.46, 95%CI 0.22–0.95, p = 0.035; OR: 0.41, 95%CI 0.20–0.85, p = 0.017, respectively). . Conclusion Our results are the first data reporting reproductive factors heterogeneity among BC molecular subtypes in Tanzania. Our findings suggest that breast-feeding may reduce the likelihood of developing luminal-A, luminal-B, and triple-negative subtypes. Meanwhile, the first full-term pregnancy after 30 years of age could increase the chance of developing luminal-A subtype, a highly prevalent subtype in Tanzania. More interventions to promote modifiable risk factors across multiple levels may most successfully reduce BC incidence in Africa.
Effective cancer treatment involves aggressive chemo-radiotherapy protocols that alter survivors' quality of life (QOL). This has recently aroused the attention not only to focus on clinical care but rather to be holistic and client-centered, looking beyond morbidity and mortality. The study assessed the QOL and associated factors among patients with cervical cancer (CC) after the completion of chemoradiotherapy.A cross-sectional analytical study was conducted at Ocean Road Cancer Institute (ORCI) from September to November 2020. A total of 323 CC patients were interviewed with a structured questionnaire of QOL, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and its cervical cancer module (EORTC QLQ-CX24). The QOL domains, socio-demographic and clinical variables were analyzed with Mann-Whitney and Kruskal-Wallis on SPSS version 23, and a P < 0.05 was considered significant.More than half (54.8%) of the CC patients had a good overall QOL. Overall, QOL was affected by education (P = 0.019), smoking (0.044), sexual partner (P = 0.000), treatment modality (P = 0.018), and time since completion of treatment (P = 0.021). Patients who underwent external beam radiation suffered from significant side effect symptoms (P < 0.05) while those who underwent combined external beam radiation and brachytherapy had higher functioning in most domains (P < 0.05).A significant improvement in QOL was observed after chemoradiotherapy and was affected by socio-demographic and clinical variables. Thus, calls for individualized care in addressing these distressing symptoms.