Clinico-pathologic characteristics and treatment outcomes in children with neuroblastoma at the Kenyatta National Hospital, Nairobi.

Objective: To determine clinical-pathologic characteristics, treatment modalities and treatment outcomes of children diagnosed with neuroblastoma. Design: Cross- sectional descriptive study based on secondary data from patient records. Setting: Records department of Kenyatta National Hospital (KNH), a tertiary teaching and referral hospital based in Nairobi. Subjects: Children aged 15 years and below, admitted with the diagnosis of neuroblastoma, between January 1997 and December 2005. Main outcome measures: Presenting clinical features, diagnostic modalities including laboratory and imaging data, treatment modalities, response to treatment and patient survival. Results: Twenty six patients were eligible for the study; 13 males and 13 females giving a M: F ratio of 1: 1. The age range was 5 days to 12 years, with a median age of five years. Abdominal swelling (53.8%), inability to walk due to bone pains,(50%), and cranial or periorbital swelling, (38.5%) were the commonest presenting features. Diagnosis of neuroblastoma was based on tissue biopsy in 50% (95% CI40.6-79.8%) of the patients, and on fine needle aspiration cytology of mass or bone marrow in the rest. Bone marrow involvement was present in 16, (75%). Anaemia,was common with 72.7% patients having a haemoglobin (HB) \u3c8g/dl at presentation. Immunohistochemistry and cytological grading were done in two, (8%), patients. Urinary vanilly l mandelic acid (VMA), screening was positive in 50% (95% CI 29.9%-70.1%). The most frequently involved organs were abdomen (88.9%), and skeleton,(84.6%). Majority of patients, (92.3%), presented with advanced stage IV disease. Three patients died before commencement of treatment. All treated patients (100%), received cytotoxic therapy. Only two patients (8.6%) had surgery as part of treatment while one, (4.3%) was treated with radiotherapy. The initial treatment regimen was similar for all the patients. Although most patients had a complete initial response to treatment, early relapse, treatment failure, death or loss to follow up of patients with progressive disease were common. Overall survival (OS) at one year and two years were 19.2% (95% CI 6.6-39.4%) and 7.7% (95% CI 0.9%-25 1%) respectively. Only one patient was alive, (also free of disease), five years after diagnosis. Conclusion: Although other clinical- pathologic findings of the patients were similar to those reported elsewhere, virtually all study patients presented with advanced stage IV disease, which would be associated with poor prognosis irrespective of quality of care. Priority must therefore be on ensuring early diagnosis and referral of patients with neuroblastoma before any other interventions can be expected to positively impact on outcome. The limited role of surgery and radiotherapy observed over the study period may be attributed to late presentation of the patients. Pathologic evaluation of patients was inadequate, to some extent due to unavailability of facilities, but extra important information could have been availed at minimal extra cost. To be at par with current internationally accepted treatment approaches that have been associated with improved survival, there is need to base choice of regimens for individual patients on clinical and readily accessible pathologic markers

Selected genes of Human herpesvirus-8 associated Kaposi’s sarcoma among patients with Human Immunodeficiency Virus-1 and Acquired Immunodeficiency Disease Syndrome

Introduction: Kaposi's sarcoma (KS) is a kind of cancer that causes flat or raised lesions containing Human herpes virus 8 (HHV8). The KS lesions are common among immunosuppressed HIV patients. Highly Active Antiretroviral (HHART) treats and prevents the development of KS. The objective of this study was to determine the presence of K1 and K15 (predominant alleles) genes in Kaposi's sarcoma-associated herpes virus (KSHV) among immunosuppressed patients due to HIV -1. Methods: this was a cross-sectional descriptive study where consecutive sampling technique was adopted to pick archived tissue blocks from the Thematic Unit of Anatomic Pathology, Department of Human Pathology, College of Health Sciences, University of Nairobi and Department of Laboratory Medicine, Histology Section, Kenyatta National Hospital Results: upon staining 81 tissue blocks with H & E, 84% (68/81) were diagnosed as KS and 16% (13/81) as KS-like. The K1 and K15 (P) genes were both detected at 88.9% (72/81) in the tissue blocks, with 95.8% (69/72) detection from KS and4.2% (3/72) from the KS-like. Conclusion: the K1 and K15 (P) genes of KSHV were present among the immunosuppressed patients with Human Immunodeficiency Virus (HIV)-1. It is important to carry out K1 and K15 (P) genes detection on tissues that are diagnosed as KS or KS-like by histology techniqu

Pattern of distribution of AIDS-related Kaposi’s sarcoma lesions in HIV patients in a referral hospital in Kenya

Background: Kaposi’s sarcoma (KS) is an angioproliferative malignancy caused by infection with human herpes virus -8 (HHV-8). The tumour has four subtypes including Classic KS, African- endemic, Iatrogenic and Acquired immunodeficiency syndrome (AIDS)-related KS. AIDS- related KS is the most common malignancy in patients with human immunodeficiency virus (HIV) infection and has variable clinical presentation with diverse distribution of lesions. Objective: To assess the pattern of distribution of KS lesions in patients with AIDS-related KS at Kenyatta National Hospital. Methods: We carried out a descriptive study on patients with HIV infection with histological diagnosis of KS. The study commenced upon approval by KNH-University of Nairobi Ethics and Research Committee. Following consent, clinical and demographic data was obtained from participants through verbal interviews and from medical records using a data capture form. Follow up was until 10 weeks. Management of patients was at the discretion of the attending clinician. Data was analyzed by a statistician using Instat Biostatistics program. Results Seventy-four participants aged between 13 to 55 years were enrolled into the study. Males were 42 (56.7%) and females 32 (43.2%). Mean age was 36.8 years. The distribution of KS lesions was variable. We demonstrate high predilection of lesions for skin and lymph nodes at 62.6%. Other sites were involved were the oral cavity 14.9%. Twenty-eight (38%) of the participants had multifocal lesions with a male predominance in skin and viscera with male to female ratio of skin 1.8:1 and viscera 7:1 respectively. Conclusion: We demonstrate reduced male: female ratio and multifocal distribution of AIDS-related KS lesions with predominance in skin and lymph nodes and male predominance in visceral lesions. Future studies should aim to determine what favours increase in, KS in women and visceral lesions in males among patients with HIV infection. Keywords: Kaposi’s Sarcoma, human immunodeficiency virus (HIV), Acquired Immunodeficiency Syndrome (AIDS

Abandonment of treatment and loss to follow up: a potential cause of treatment failure in patients with AIDS-related Kaposi’s sarcoma

Background: Management of patients with cancer is complex, multi-disciplinary, longitudinal and costly. Abandonment of treatment by patients and loss to follow up is a common scenario, especially in resource poor countries and severely compromises health outcomes. Objective: To assess the commitment to drug treatment protocol of patients with Acquired Immunodeficiency Syndrome (AIDS)-Related Kaposi’s Sarcoma at Kenyatta National Hospital, Kenya, over a 10 week period . Methods: The study design was prospective, observational, cross-sectional period prevalence study on patients infected with human immunodeficiency virus (HIV) with Kaposi’s sarcoma. Patients with histological diagnosis of Kaposi’s sarcoma were sequentially enrolled into the study as they attended either the Haematology or Radiotherapy clinic or during their admission in the wards. The choice of the treatment protocol was left at the discretion of the attending physician. A pretested data collection form was used to collect demographic and clinical information about the patients, including treatments prescribed and completion of follow up. Results: A total of 74 patients were enrolled into the study, 42 (56.8%) males and 32 (43.2%) females. The age ranged between 13 years to 55 years. Their treatment protocols included: Vincristine only, Vincristine plus Bleomycin, Vincristine plus Bleomycin plus Doxorubicin, Radiotherapy plus Vincristine and Radiotherapy only. Few of the patients were not assigned any antitumor treatment. Antiemetic and other conventional medicines were also prescribed when necessary. Fifty four (73%) of the patients abandoned treatment, five (6.8%) died, 15(20.3%) continued to attend clinic over the 10 week period.  There was no significant association between sex and outcome (p=0.661). Discussion: The results of this study demonstrate that abandonment of treatment is a major problem among patients on treatment for cancer in Kenyatta National Hospital in Kenya. Abandonment of treatment heavily contributes to poor clinical outcome hence complicating the burden of cancer in the country. It is therefore important to develop and establish follow-up systems to improve adherence to treatment for the cancer patients at Kenyatta National Hospital. Key words: Abandonment of treatment, Loss to follow up, AIDS-Related Kaposi’s Sarcom

HPV Infection and EGFR Activation/Alteration in HIV-Infected East African Patients with Conjunctival Carcinoma

Background There has been substantial growth in the numbers of patients with conjunctival squamous cell carcinoma infected with HIV in East Africa. The natural history of the conjunctival squamous cell carcinoma appears to be unique in this region of the world, but the etiologic mechanism unclear and therapeutic options limited. This research was carried out to determine if conjunctival squamous cell carcinoma harbors human papillomavirus DNA and is associated with activation of the EGFR signaling pathway. Positive findings would identify etiologic causes and provide clinical guidance to improve treatment. Methods/Findings Expression of p-MAPK/MAPK, p-Akt/Akt and p-EGFR/EGFR in cell nuclei and cytoplasm of 38 FFPE specimens were assessed by immunohistochemistry; HPV genotype was detected by qPCR assay; EGFR mutation was assessed by DNA sequencing analysis; and EGFR mRNA expression was measured using relative qPCR. Statistical analyses included two-sided Fisher exact test or chi-square test, Spearman correlation coefficient and ANOVA. HPV 18 was found in 61% of samples, with HPV 16 double-genotype in 6 patients (16%). Immunohistochemistry and qPCR data suggest that activation and expression of the EGFR signaling pathway is related to disease progression of conjunctival cancer. The associations between cytoplasmic p-MAPK, cytoplasmic p-Akt and tumor invasiveness were significant (p = 0.05 or 0.028). Nuclear p-EGFR appeared only in invasive tumors. A significant positive association between EGFR expression and disease invasiveness was observed (p = 0.01). A SNP in 10 patients and one missense mutation were found within EGFR tyrosine kinase domain. Statistical analysis indicates that patients with measurable EGFR expression more likely harbor EGFR mutations, compared to those with negative EGFR expression (35.3% vs. 0%). Conclusions/Significance We conclude that HPV types 16/18 infection is frequent in East African patients with AIDS-associated squamous cell carcinoma of the conjunctiva. EGFR activation/alteration may contribute to and sustain the high prevalence of this cancer. Our findings hint that adoption of HPV vaccination strategies may impact the incidence of conjunctival carcinoma. Agents that target the EGFR pathway may have potential therapeutic benefit

Building capacity in implementation science research training at the University of Nairobi.

BACKGROUND: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science. METHODS: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science. RESULTS: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision. CONCLUSIONS: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula

Developing Clinical Strength-of-Evidence Approach to Define HIV-Associated Malignancies for Cancer Registration in Kenya

Background Sub-Saharan Africa cancer registries are beset by an increasing cancer burden further exacerbated by the AIDS epidemic where there are limited capabilities for cancer-AIDS match co-registration. We undertook a pilot study based on a “strength-of-evidence” approach using clinical data that is abstracted at the time of cancer registration for purposes of linking cancer diagnosis to AIDS diagnosis. Methods/Findings The standard Nairobi Cancer Registry form was modified for registrars to abstract the following clinical data from medical records regarding HIV infection/AIDS in a hierarchal approach at time of cancer registration from highest-to-lowest strength-of-evidence: 1) documentation of positive HIV serology; 2) antiretroviral drug prescription; 3) CD4+ lymphocyte count; and 4) WHO HIV clinical stage or immune suppression syndrome (ISS), which is Kenyan terminology for AIDS. Between August 1 and October 31, 2011 a total of 1,200 cancer cases were registered. Of these, 171 cases (14.3%) met clinical strength-of-evidence criteria for association with HIV infection/AIDS; 69% (118 cases were tumor types with known HIV association – Kaposi’s sarcoma, cervical cancer, non-Hodgkin’s and Hodgkin’s lymphoma, and conjunctiva carcinoma) and 31% (53) were consistent with non-AIDS defining cancers. Verifiable positive HIV serology was identified in 47 (27%) cases for an absolute seroprevalence rate of 4% among the cancer registered cases with an upper boundary of 14% among those meeting at least one of strength-of-evidence criteria. Conclusions/Significance This pilot demonstration of a hierarchal, clinical strength-of-evidence approach for cancer-AIDS registration in Kenya establishes feasibility, is readily adaptable, pragmatic, and does not require additional resources for critically under staffed cancer registries. Cancer is an emerging public health challenge, and African nations need to develop well designed population-based studies in order to better define the impact and spectrum of malignant disease in the backdrop of HIV infection

HPV Infection and EGFR Activation/Alteration in HIV-Infected East African Patients with Conjunctival Carcinoma

Background There has been substantial growth in the numbers of patients with conjunctival squamous cell carcinoma infected with HIV in East Africa. The natural history of the conjunctival squamous cell carcinoma appears to be unique in this region of the world, but the etiologic mechanism unclear and therapeutic options limited. This research was carried out to determine if conjunctival squamous cell carcinoma harbors human papillomavirus DNA and is associated with activation of the EGFR signaling pathway. Positive findings would identify etiologic causes and provide clinical guidance to improve treatment. Methods/Findings Expression of p-MAPK/MAPK, p-Akt/Akt and p-EGFR/EGFR in cell nuclei and cytoplasm of 38 FFPE specimens were assessed by immunohistochemistry; HPV genotype was detected by qPCR assay; EGFR mutation was assessed by DNA sequencing analysis; and EGFR mRNA expression was measured using relative qPCR. Statistical analyses included two-sided Fisher exact test or chi-square test, Spearman correlation coefficient and ANOVA. HPV 18 was found in 61% of samples, with HPV 16 double-genotype in 6 patients (16%). Immunohistochemistry and qPCR data suggest that activation and expression of the EGFR signaling pathway is related to disease progression of conjunctival cancer. The associations between cytoplasmic p-MAPK, cytoplasmic p-Akt and tumor invasiveness were significant (p = 0.05 or 0.028). Nuclear p-EGFR appeared only in invasive tumors. A significant positive association between EGFR expression and disease invasiveness was observed (p = 0.01). A SNP in 10 patients and one missense mutation were found within EGFR tyrosine kinase domain. Statistical analysis indicates that patients with measurable EGFR expression more likely harbor EGFR mutations, compared to those with negative EGFR expression (35.3% vs. 0%). Conclusions/Significance We conclude that HPV types 16/18 infection is frequent in East African patients with AIDS-associated squamous cell carcinoma of the conjunctiva. EGFR activation/alteration may contribute to and sustain the high prevalence of this cancer. Our findings hint that adoption of HPV vaccination strategies may impact the incidence of conjunctival carcinoma. Agents that target the EGFR pathway may have potential therapeutic benefit

Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.

The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors') while 20% do not (termed 'non-secretors'). Furthermore, there are disease conditions that are associated with secretor status.To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya.This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis.Out of the 280 participants, 212 (75.7%) were secretors and 68 (24.3%) were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7%) versus HIV un-infected secretors (71.8%) (p = 0.029) Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%), in comparison to B (12/39 = 33.3%: p = 0.066), AB (3/9 = 33.3%: p = 0.355), and O secretors (36/112 = 32.1%: p = 0.028).This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population in a Kenyan population. These findings suggest the non-secretor phenotype may confer a certain degree of protection against HIV infection