Screening of Depression Among Medical Outpatients Visiting the University Teaching Hospital of Kigali, Rwanda.

Background: Depression is a significant global public health concern, affecting individuals across different age groups and cultural backgrounds. However, screening for depression remains an essential but often neglected aspect of healthcare, particularly in outpatient settings. This study aimed to assess the prevalence of depression among outpatients visiting the internal medicine department of the University Teaching Hospital of Kigali in Rwanda and evaluate the feasibility of implementing a depression screening program in this setting. Methods: An institution-based cross-sectional study design was employed, involving 300 adult medical outpatients through convenience sampling, aged 18 years and above, who visited the internal medicine department between October 7 to November 6, 2019. The Patient Health Questionnaire-9 (PHQ-9) was used as the screening tool to assess depressive symptoms. Additionally, socio-demographic and clinical data were collected to explore potential risk factors associated with depression using a binary logistic regression model. Results: A high prevalence of depression was identified among internal medicine outpatients, with 45.7% of participants screened positive for depression, with moderate, moderately severe, and severe depression accounting for 21%, 17%, and 8%, respectively. The following factors were significantly associated with positive screening for depression: lack of formal education (OR=4.463, p=0.011, 95% CI= [1.410; 14.127]), secondary education (OR=3.402, p=0.003, 95% CI= [1.517; 7.630]), low-income (OR=2.392, p=0.049, 95% CI= [1.003; 5.706]) and headache as a chief complaint (OR=3.611, p=0.001, CI= [1.718; 7.591]). Conclusion: This study highlights the high prevalence of depression among medical outpatients. Due to the stigma associated with mental health, patients frequently seek help for physical symptoms such as headaches and other bodily complaints rather than mental health concerns. Introducing routine depression screening in medical departments could potentially facilitate early identification, and intervention, and lead to improved patient care. Future research should focus on evaluating such screening programs' effectiveness and long-term outcomes in resource-limited settings like Rwanda.

The spectrum of TP53 mutations in Rwandan patients with gastric cancer.

BACKGROUND: Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. RESULTS: Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon-intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. CONCLUSIONS: Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.

TP53 mutations in Romanian patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has been ranked as the second most deadly cancer and the third most diagnosed cancer cases for the year 2020. Specifically for Romania, the number of CRC-related deaths in 2019 was estimated at 6307 people, with a standardized mortality rate of 33.8 per 100,000 inhabitants. Although the tumor protein 53 (TP53) gene is intensively studied, there are few data on TP53 mutations in Romanian CRC. Furthermore, since genetic alterations may show geographical differences, our study aimed to analyze the clinical status and TP53 somatic variation in Romanian CRC patients. SUBJECTS AND METHODS: DNA from 40 randomly selected cases of CRC was extracted from formalin-fixed paraffin-embedded tissues and sequenced using direct Sanger sequencing techniques, and variants were annotated according to the recommendations of the Human Genome Variation Society. Novel variants were analyzed using MutationTaster2021 to predict their effects. RESULTS: The mean age was 63.6 years (range 33-85 years) with a male to female ratio of 2.3. More than 45% (18/40) had an advanced cancer stage (≥ stage III). Mutations were found in 21/40 cases (52.5%), with one case having two mutations, giving a total of twenty-two mutations in the TP53 coding DNA. These mutations include 3 (13.6%) insertion-deletion mutations, two of which are novel frameshift mutations: c.165delT (in exon 4) and c.928_935dup (in exon 9), both of which are predicted to lead to nonsense-mediated mRNA decay and are classified as deleterious. The remaining 19 (86.36%) were substitution mutations: 1 nonsense and 18 (81.8%) missense mutations, with G > A (n = 7/19; 36.8%) and C > T (n = 6/19; 31.5%) transitions being the most common. The G > T transversion was found in 21.05% (4/19) of the substitution mutations. CONCLUSION: We have described two novel frameshift mutations in TP53. The discovery of novel mutations following the efforts of The Cancer Genome Atlas and other large-scale cancer genome sequencing projects may be further evidence of the heterogeneous nature of mutations in cancer and may indicate that the identification of carcinogenic mutations is not yet saturated. Further sequencing is therefore needed, especially in less studied populations. Importantly, consideration of their geographical environment will shed light on population-specific carcinogenesis.

Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer.

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

The use of Vsee videoconferencing for live telepathology in Rwanda, a potential solution for resource-limited area.

Objective: The shortage of pathologists is a worldwide problem that is more severe in Africa. One of the solutions is the use of telepathology (TP); however, most of the TP systems are expensive and unaffordable in many developing countries. At the University Teaching Hospital of Kigali, Rwanda, we assessed the possibility of combining commonly available laboratory tools into a system that can be used for diagnostic TP using Vsee videoconferencing. Methodology: Using an Olympus microscope (with a camera) operated by a laboratory technologist, histologic images were transmitted to a computer whose screen was shared, using Vsee, with a remotely located pathologist who made the diagnoses. Sixty consecutive small biopsies (≤6 glass slides) from different tissues were examined to make a diagnosis using live Vsee-based videoconferencing TP. Vsee-based diagnoses were compared to pre-existing light microscopy-based diagnoses. Percent agreement and unweighted Cohen's kappa coefficient of the agreement were calculated. Results: For agreement between conventional microscopy-based and Vsee-based diagnoses, we found an unweighted Cohen's kappa of 0.77 ± 0.07SE with a 95% CI of 0.62-0.91. The perfect percent agreement was 76.6% (46 of 60). Agreement with minor discrepancy was 15% (9 of 60). There were 2 cases of major discrepancy (3.30%). We were unable to make a diagnosis in 3 cases (5%) because of poor image quality related to the instantaneous internet connectivity problems. Conclusion: This system provided promising results. However, additional studies to assess other parameters which can affect its performance are needed before this system can be considered an alternative method of providing TP services in resource-limited settings.

Non-CpG sites preference in G:C > A:T transition of TP53 in gastric cancer of Eastern Europe (Poland, Romania and Hungary) compared to East Asian countries (China and Japan).

AIM: Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. SUBJECTS AND METHOD: In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. RESULTS: The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. CONCLUSION: The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Knowledge, Barriers and Motivators to Cervical Cancer Screening in Rwanda: A Qualitative Study.

Background: Cervical cancer is a global public health problem with marked geographical disparity. High morbidity and mortality rates in developing countries are associated with low screening rates. In 2020, in Rwanda, 3.7 million women aged 15-59 years were at risk of developing cervical cancer, the most commonly diagnosed female cancer in Rwanda. Despite Rwanda being the first African country to vaccinate against human papilloma virus with a three-dose regimen vaccination coverage of nearly 93% in the target population of girls aged <15 years, and having established cervical cancer screening program, recent studies have found low screening rates. Our study sought to determine knowledge, motivators and barriers of cervical cancer screening. Methods: We conducted a qualitative descriptive study; using focus group interview in an urban health facility (Muhima district hospital) and a rural health center (Nyagasambu health center) offering cervical screening services in Rwanda. Participants were women seeking these services and other women attending the health facility for any reason, and female staff working in these facilities. Interviews were recorded and transcribed, and data were analyzed using content analysis. Results: Thirty women participated in focus group interview, with an average age of 39 years. Many of women showed knowledge about cervical cancer existence and prevention methods. However, fear for pain, lack of knowledge about screening, how and where the screening was done, and concern for privacy were recurring subthemes. Some participants also mentioned lack of health insurance as a barrier for cervical cancer screening. Conclusion: Barriers to uptake cervical cancer screening services in Rwanda are related to poor information about cervical cancer and the importance of screening as well as non-adherence to medical insurance. Population sensitization through campaign and community outreach activities could have a positive impact on increasing the usage of cervical cancer screening in Rwanda.

Exploring Perceptions and Acceptance of Minimally Invasive Tissue Sampling among Bereaved Relatives and Health-Care Professionals in Rwanda.

PURPOSE: In most low- and lower middle-income countries (LMICs), minimally invasive tissue sampling (MITS) is a relatively new procedure for identifying the cause of death (CoD). This study aimed to explore perceptions and acceptance of bereaved families and health-care professionals regarding MITS in the context of MITS initiation in Rwanda as an alternative to clinical autopsy. METHODS: This was a qualitative phenomenological study with thematic analysis. Participants were bereaved relatives (individual interviews) and health-care professionals (focus-group discussions) involved in MITS implementation. It was conducted in the largest referral and teaching hospital in Rwanda. RESULTS: Motivators of MITS acceptance included eagerness to know the CoD, noninvasiveness of MITS, trust in medics, and the fact that it was free. Barriers to consent to MITS included inadequate explanations from health-care professionals, high socioeconomic status, lack of power to make decisions, and lack of trust in medics. Health-care professionals perceived both conventional autopsy and MITS as gold-standard procedures in CoD determination. They recommended including MITS among hospital services and commended the post-MITS multidisciplinary discussion panel in CoD determination. They pointed out that there might be reticence in approaching bereaved relatives to obtain consent for MITS. Both groups of participants highlighted the issue of delay in releasing MITS results. CONCLUSION: Both health-care professionals and bereaved relatives appreciate that MITS is an acceptable procedure to include in routine hospital services. Dealing with barriers met by either group is to be considered in the eventual next phases of MITS implementation in Rwanda and similar sociocultural contexts.

Tuberculosis of the Left Calcaneum and Collapsed Right Femoral Head: A Case Report.

INTRODUCTION: Tuberculosis (TB), one of the oldest diseases known to affect humans, is caused by the bacteria Mycobacterium tuberculosis. The disease usually affects the lungs, although, in up to one-third of cases, other organs are involved. TB of the bone mimics other clinical conditions such as chronic osteomyelitis, Madura mycosis and actinomycosis. CASE REPORT: A fifth child and last-born girl, in a family of living four children, aged 9 years, consulted Kigali University Teaching Hospital (CHUK) on December 7, 2017, from Kibuye Referral Hospital (Western of Rwanda) for ulcerated, infected left heel with swollen foot 4 months before our consultation. Physical examination revealed a patient with swollen and tender foot discharging serous bloody fluids accompanied by inability to stand with a painful right hip. Small left inguinal lymph nodes were present. Blood work-up, computed tomography scan of the left foot, and an incisional biopsy at the level of the left calcaneus were performed and revealed extrapulmonary TB. The histopathological features for TB were scanty, but the high index suspicion of possible extrapulmonary TB led to the confirmation of the diagnosis using auramine-rhodamine special stain. Anti-TB therapy for 12 months course was initiated and the monthly follow-up for 11 months was done. CONCLUSION: Although calcaneal TB is very rare, in countries with high incidence of TB, clinicians must have a high suspicion index and skeletal TB must be included in differential diagnosis of bone masses whenever possible bone mass biopsy and special staining technique in addition to most common diagnosis means should be done to rule out the possibility of bone TB.

Occurrence of Helicobacter Pylori in Specimens of Chronic Gastritis and Gastric Adenocarcinoma Patients: A Retrospective Study at University Teaching Hospital, Kigali, Rwanda.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is the major cause of gastroduodenal diseases in populations of different ages. We conducted aretrospective studyusing archived tissue samples to determine the prevalence of H. pylori infection among patients diagnosed with gastritis and gastric adenocarcinoma by histopathology cases in one hospital in Rwanda. MATERIALS AND METHODS: Cases of chronic gastritis and gastric adenocarcinoma histologically diagnosed in a tertiary hospital in Rwanda over the period of 2016-2018 were studied for the presence of H. pylori using immunohistochemistry. Diagnosis of positive cases considered immunoreactivity as well as bacterial morphology, including spiral, rod-shaped, angulated and coccoid forms. RESULTS: Three hundred and seven cases were included in this study; chronic gastritis and gastric adenocarcinoma representing 39% and 61%, respectively. The overall frequency of H. pylori infection was 77.5% (80% among chronic gastritis cases versus 76% among gastric adenocarcinoma cases). Prevalence of H. pylori infection in chronic gastritis and adenocarcinoma did not significantly associate with age and sex. CONCLUSION: The prevalence of H. pylori was high among chronic gastritis and gastric adenocarcinoma cases in Rwanda. Pathologists should investigate the presence of H. pylori in gastric biopsies. Our data shows immunohistochemistry method is feasible and adequate to facilitate detection of H. pylori, which may guide timely treatment.

Pathology Characteristics of Lymphomas in Rwanda: A Retrospective Study.

BACKGROUND: Lymphomas have been a global challenge for many decades and despite measures for prevention and management, the incidence continues to increase. There are two main categories, which are Non-Hodgkin's Lymphomas and Hodgkin's Lymphomas and most common etiologies are environmental, genetic alteration, radiation and some viruses. OBJECTIVE: To describe pathology characteristics of lymphomas in Rwanda based on Hematoxylin and Eosin stained glass slides and immuno histo chemistry, and classify them according to clinical aggressiveness. PATIENTS AND METHODS: We conducted a retrospective observational and descriptive study from January 2013 to December 2019. Lymphoma cases were retrieved together with relevant clinical and pathological information, and reviewed by independent pathologists. Histological diagnosis was classified according to the 2008 World Health Organization system in order to assign clinical aggressiveness of the lymphoma. RESULTS: Three hundred and six lymphoma cases were enrolled. Males contributed to 57% of all reviewed case, and slightly over 50% were young aged ≤35 years. Approximately 191 (62%) of cases were nodal lymphomas. Approximately one fifth (18%) of lymphoma cases were HIV positive. Most 213(70%) cases were Non-Hodgkin's Lymphomas of aggressive forms 164(77%). Among 164 cases of aggressive Non-Hodgkin's Lymphomas, diffuse large B cell lymphoma was the leading subtype 91(55.5%), followed by solid lymphoblastic lymphoma 32(19.5%) and Burkitt lymphoma 17(10.4%). Among all Hodgkin lymphoma cases, 90(97%) were classical Hodgkin lymphomaof nodular sclerosis subtype. Hodgkin lymphoma patients were younger compared to Non-Hodgkin's Lymphomas patients (mean age of 24.78±16.3 years versus 38.6±22. 5years, p=.000). CONCLUSION: Substantial proportion of Lymphomapatients in Rwanda were also HIV positive. Interestingly, Non-Hodgkin's Lymphomas in Rwanda are predominated by the most aggressive forms, and these mostly affect a younger population. Optimal characterisation of such cases, using advanced methods, is recommended.

Osteoblastic Osteosarcoma Arising beneath an Osteochondroma in an 11-Year-Old Male with Multiple Hereditary Exostoses.

INTRODUCTION: Multiple hereditary exostoses (MHE) is a rare autosomal dominant disorder characterized by the presence of multiple skeletal deformities. They are painless slow-growing lesions. Malignant transformation tends to occur later in adulthood and has only been seen in 1-5% of patients. OBJECTIVE: We describe the clinical, radiological, and pathological characteristics of a child with MHE who developed osteoblastic osteosarcoma beneath an osteochondroma. CASE PRESENTATION: An 11-year-old male Rwandan presented to our hospital with a two-week history of a dull persistent pain in his left distal femur and loss of weight and appetite. There was no relief with pain killers. He was a known case of multiple hereditary exostoses diagnosed at age 3. He began experiencing mild symptoms 6 months prior to admission which worsened in the last two weeks prior to his admission. On examination, he had multiple palpable bony swellings bilaterally on the proximal humeri and distal femurs. X-rays showed multiple exostoses and MRI showed a lesion with heterogeneous signal intensities that suggested malignant transformation. At surgery, a necrotic lesion beneath the exostosis was excised and sent for histopathological analysis which confirmed osteochondroma with an osteoblastic osteosarcoma in the marrow cavity. Chemotherapy and limb-salvaging surgery were done and he has recovered well. CONCLUSION: Osteosarcomas arising at sites of MHE have not been previously reported in Africa. These tumors rarely undergo malignant transformation.