Publications by authors named "Nestory Masalu"

41 Publications

Inverse association of falciparum positivity with endemic Burkitt lymphoma is robust in analyses adjusting for pre-enrollment malaria in the EMBLEM case-control study.

Infect Agent Cancer 2021 Jun 7;16(1):40. Epub 2021 Jun 7.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Infections and Immunoepidemiology Branch, 9609 Medical Center Dr, Rm. 6E-118, MSC 3330, Bethesda, MD, 20892, USA.

Background: Falciparum and endemic Burkitt lymphoma (eBL) are co-endemic in Africa, but the malaria experience in eBL patients is unknown. A lower prevalence of falciparum has been reported in eBL patients, but those results are anecdotally attributed to pre-enrollment anti-malaria treatment.

Methods: We studied 677 eBL patients and 2920 community controls aged 0-15 years enrolled in six regions in Uganda, Tanzania, and Kenya during 2010-2016. Falciparum was diagnosed using thick blood film microscopy (TFM) and antigen-capture rapid diagnostic tests (RDTs). Guardians of the children answered a 40-item structured questionnaire about their child's pre-enrollment lifetime malaria history and treatment, demographics, socioeconomics, animal exposures, fevers, and hospitalizations. We utilized exploratory factor analysis to reduce the 40 questionnaire variables into six factors, including Inpatient malaria and Outpatient malaria factors that were surrogates of pre-enrollment anti-malaria treatment. The six factors accounted for 83-90% of the variance in the questionnaire data. We calculated odds ratios and 95% confidence intervals (OR 95% CI) of association of eBL with falciparum positivity, defined as positive both on TFM or RDTs, or only RDTs (indicative of recent infection) or TFM (indicative of current falciparum infection) versus no infection, using multivariable logistic regression, controlling for group of age (0-2, 3-5, 6-8, 9-11 and 12-15 years), sex, and study site and the afore-mentioned pre-enrollment factors.

Results: The prevalence of falciparum infection was 25.6% in the eBL cases and 45.7% in community controls (aOR = 0.43, 95% CI: 0.40, 0.47; P < 0.0001). The results were similar for recent falciparum infection (6.9% versus 13.5%, aOR = 0.44, 95% CI: 0.38, 0.50; P < 0.0001) and current falciparum infection (18.7% versus 32.1%, aOR = 0.47, 95% CI: 0.43, 0.51; P < 0.0001). These aORs for any, recent and current falciparum infection did not change when we adjusted for pre-enrollment factors (aORs = 0.46, =0.44, and = 0.51, respectively) were significantly lower in stratified analysis for any infection in children < 5 years (aOR = 0.46; 95% CI: 0.29, 0.75) or ≥ 10 years (aOR = 0.47; 95% CI: 0.32, 0.71).

Conclusion: Our study results reduce support for pre-enrollment antimalaria treatment as a sole explanation for the observed lower falciparum prevalence in eBL cases and open a space to consider alternative immunology-based hypotheses.
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http://dx.doi.org/10.1186/s13027-021-00377-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186042PMC
June 2021

Invasive breast Cancer treatment in Tanzania: landscape assessment to prepare for implementation of standardized treatment guidelines.

BMC Cancer 2021 May 10;21(1):527. Epub 2021 May 10.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Office E6150, Baltimore, MD, 21205, USA.

Background: Incidence of breast cancer continues to rise in low- and middle-income countries, with data from the East African country of Tanzania predicting an 82% increase in breast cancer from 2017 to 2030. We aimed to characterize treatment pathways, receipt of therapies, and identify high-value interventions to increase concordance with international guidelines and avert unnecessary breast cancer deaths.

Methods: Primary data were extracted from medical charts of patients presenting to Bugando Medical Center, Tanzania, with breast concerns and suspected to have breast cancer. Clinicopathologic features were summarized with descriptive statistics. A Poisson model was utilized to estimate prevalence ratios for variables predicted to affect receipt of life-saving adjuvant therapies and completion of therapies. International and Tanzanian guidelines were compared to current care patterns in the domains of lymph node evaluation, metastases evaluation, histopathological diagnosis, and receptor testing to yield concordance scores and suggest future areas of focus.

Results: We identified 164 patients treated for suspected breast cancer from April 2015-January 2019. Women were predominantly post-menopausal (43%) and without documented insurance (70%). Those with a confirmed histopathology diagnosis (69%) were 3 times more likely to receive adjuvant therapy (PrR [95% CI]: 3.0 [1.7-5.4]) and those documented to have insurance were 1.8 times more likely to complete adjuvant therapy (1.8 [1.0-3.2]). Out of 164 patients, 4% (n = 7) received concordant care based on the four evaluated management domains. The first most common reason for non-concordance was lack of hormone receptor testing as 91% (n = 144) of cases did not undergo this testing. The next reason was lack of lymph node evaluation (44% without axillary staging) followed by absence of abdominopelvic imaging in those with symptoms (35%) and lack of histopathological confirmation (31%).

Conclusions: Patient-specific clinical data from Tanzania show limitations of current breast cancer management including axillary staging, receipt of formal diagnosis, lack of predictive biomarker testing, and low rates of adjuvant therapy completion. These findings highlight the need to adapt and adopt interventions to increase concordance with guidelines including improving capacity for pathology, developing complete staging pathways, and ensuring completion of prescribed adjuvant therapies.
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http://dx.doi.org/10.1186/s12885-021-08252-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108449PMC
May 2021

An initiative to assess the quality of Tanzanian cervical cancer specimens for HPV and telomerase detection.

Pathol Res Pract 2021 Feb 18;218:153344. Epub 2021 Jan 18.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address:

The aim of our study was to assess the quality of Tanzanian cervical cancer specimens, evaluating telomerase alterations and human papilloma virus (HPV) infection in relation to histopathological characteristics since these biomarkers are not routinely analyzed. Thirty-two Tanzanian women with invasive cervical cancer were included in the study. Histopathological classification and all the analyses on tissue, including TERT immunohistochemistry, were performed at IRST IRCCS (Meldola, Italy). HPV typization was performed by pyrosequencing. FHACT™ was used to identify chromosomal aberrations. Nonparametric ranking statistics were used. The majority (75 %) of the cases analyzed were squamous carcinoma, while 12.5 % were adenocarcinoma. The presence of HPV infection was confirmed in 26/27 (96.3 %) cases. A high percentage of patients (88 %) were infected with HPV16 of whom 12 (44.4 %) with African type 1, and 4 (14.8 %) with African type 2. TERT expression evaluated in the entire case series showed a median H-score of 130 (range 3-270), with only one negative case. 88 % of the FISH-evaluable samples showed an amplification of the chromosomal region 3q26 (TERC) and/or 5p15, and 20q13, associated with a higher median expression of TERT (P = 0.0226). Despite pre-analytical problems in terms of sample fixation, we showed that the search for biomarkers such as HPV and telomerase is feasible in Tanzanian tissue. These markers could be important risk-stratification tools in this population.
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http://dx.doi.org/10.1016/j.prp.2021.153344DOI Listing
February 2021

Delays Experienced by Patients With Pediatric Cancer During the Health Facility Referral Process: A Study in Northern Tanzania.

JCO Glob Oncol 2020 11;6:1757-1765

Department of Oncology, Bugando Medical Centre, Mwanza, Tanzania.

Purpose: It is estimated that 50%-80% of patients with pediatric cancer in sub-Saharan Africa present at an advanced stage. Delays can occur at any time during the care-seeking process from symptom onset to treatment initiation. Referral delay, the time from first presentation at a health facility to oncologist evaluation, is a key component of total delay that has not been evaluated in sub-Saharan Africa.

Methods: Over a 3-month period, caregivers of children diagnosed with cancer at a regional cancer center (Bugando Medical Centre [BMC]) in Tanzania were consecutively surveyed to determine the number and type of health facilities visited before presentation, interventions received, and transportation used to reach each facility.

Results: Forty-nine caregivers were consented and included in the review. A total of 124 facilities were visited before BMC, with 31% of visits (n = 38) resulting in a referral. The median referral delay was 89 days (mean, 122 days), with a median of two facilities (mean, 2.5 facilities) visited before presentation to BMC. Visiting a traditional healer first significantly increased the time taken to reach BMC compared with starting at a health center/dispensary (103 236 days; = .02). Facility visits in which a patient received a referral to a higher-level facility led to significantly decreased time to reach BMC ( < .0001). Only 36% of visits to district hospitals and 20.6% of visits to health centers/dispensaries yielded a referral, however.

Conclusion: The majority of patients were delayed during the referral process, but receipt of a referral to a higher-level facility significantly shortened delay time. Referral delay for pediatric patients with cancer could be decreased by raising awareness of cancer and strengthening the referral process from lower-level to higher-level facilities.
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http://dx.doi.org/10.1200/GO.20.00407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713565PMC
November 2020

Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya.

Malar J 2020 Jul 28;19(1):239. Epub 2020 Jul 28.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Endemic Burkitt lymphoma (eBL) is an aggressive B cell non-Hodgkin lymphoma associated with antigenic stimulation from Plasmodium falciparum malaria. Whether eBL risk is related to malaria parasite density is unknown. To address this issue, children with eBL, asymptomatic and clinical malaria, as a surrogate of malaria parasite density, were assessed.

Methods: Malaria-related laboratory results (parasite density, haemoglobin, platelet count, and white cell count [WBC]) count) were compiled for 4019 eBL cases and 80,532 subjects evaluated for asymptomatic malaria or clinical malaria (severe malaria anaemia, hyperparasitaemia, cerebral malaria, malaria prostration, moderate malaria, and mild malaria) in 21 representative studies published in Africa (mostly East Africa) and 850 eBL cases and 2878 controls with primary data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) case-control study in Uganda, Tanzania, and Kenya. The average values of malaria-related laboratory results were computed by condition and trends across single-year age groups were assessed using regression and spline models.

Results: Overall, malaria infection or malaria was diagnosed in 37,089 of children compiled from the literature. Children with eBL and asymptomatic parasitaemia/antigenaemia, but not those with clinical malaria, were closest in their mean age (age 7.1-7.2 vs. 7.4-9.8 years), haemoglobin level (10.0-10.4 vs. 11.7-12.3 g/dL), malaria parasite density (2800 vs. 1827-7780 parasites/µL), platelet count (347,000-353,000 vs. 244,000-306,000 platelets/µL), and WBC count (8180-8890 vs. 7100-7410 cells/µL). Parasite density in these two groups peaked between four to five years, then decreased steadily thereafter; conversely, haemoglobin showed a corresponding increase with age. Children with clinical malaria were markedly different: all had an average age below 5 years, had dramatically elevated parasite density (13,905-869,000 parasites/µL) and dramatically decreased platelet count (< 159,000 platelets/µL) and haemoglobin (< 7 g/dL).

Conclusions: eBL and asymptomatic parasitaemia/antigenaemia, but not clinical malaria, were the most similar conditions with respect to mean age and malaria-related laboratory results. These results suggest that children with asymptomatic parasitaemia/antigenaemia may be the population at risk of eBL.
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http://dx.doi.org/10.1186/s12936-020-03312-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385955PMC
July 2020

Cancer incidence and treatment utilization patterns at a regional cancer center in Tanzania from 2008-2016: Initial report of 2,772 cases.

Cancer Epidemiol 2020 08 10;67:101772. Epub 2020 Jul 10.

Bugando Medical Centre, Mwanza, Tanzania; Duke Global Health Institute, Duke University, Durham, NC, USA; Department of Pediatric Hematology/Oncology, Duke University, Durham, NC, USA. Electronic address:

Purpose: To describe cancer incidence and treatment utilization patterns at the regional cancer referral center for the Lake Zone of northwestern Tanzania from 2008 to 2016.

Methods: This descriptive, retrospective study reviewed all cancer cases recorded in the Bugando Cancer Registry (BCR), a clinical and pathology based registry at the only cancer referral hospital in the region. Primary tumor site, method of diagnosis, HIV status, and cancer treatment were reported. Using census data, the 2012 GLOBOCAN estimates for Tanzania were scaled to the Lake Zone and adjusted for 2016 population growth. These estimates were then compared to BCR cases using one-sample tests of proportion.

Results: A total of 2772 cases were reported from 2008-2016. Among these, the majority of cases (82.5 %, n = 2286) were diagnosed among adults. Most cases (85 %, n = 1923) were diagnosed by histology or cytology. Among adults, the most common cancers diagnosed were cervix (22.7 %, n=520), breast (12.6 %, n=288), and prostate (8.5 %, n=195). Among children, the most common cancers were non-Burkitt non-Hodgkin lymphoma (17.3 %, n=84), Burkitt lymphoma (16.5 %, n=80), and Wilms tumor (14.6 %, n=71). The 1116 BCR cases represent 12.2 % of the 9165 expected number of cancer cases for the Lake Zone (p < 0.001). 1494 cases (53.9 %) received some form of treatment - surgery, chemotherapy, radiation, or hormone therapy - while 1278 cases (46.1 %) had no treatment recorded.

Conclusions: This comprehensive report of the BCR reveals cancer epidemiology and treatment utilization patterns typical of hospitals in low-resource settings. Despite being the only cancer center in the Lake Zone, BMC evaluates a small percentage of the expected number of cancer patients for the region. The BCR remains an important resource to guide clinical care and academic activities for the Lake Zone.
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http://dx.doi.org/10.1016/j.canep.2020.101772DOI Listing
August 2020

Understanding women's perspectives on breast cancer is essential for cancer control: knowledge, risk awareness, and care-seeking in Mwanza, Tanzania.

BMC Public Health 2020 Jun 15;20(1):930. Epub 2020 Jun 15.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Background: Breast Cancer is the most common cancer in women worldwide. Since 2008, Mwanza, Tanzania, has worked to provide comprehensive cancer services through its Zonal consultant hospital. New national guidelines focused on clinical breast exam requires that women be aware of and seek care for breast concerns. Therefore, this study aims to understand breast cancer awareness in Mwanza and describe women-level barriers, care-seeking behavior, and perspectives on breast cancer.

Methods: A community-based survey was administered to conveniently sampled women aged 30 and older to assess women's perspectives on breast cancer and care-seeking behavior.

Results: Among 1129 women with a median age of 37 (IQR: 31-44) years, 73% have heard of cancer and 10% have received breast health education. Women self-evaluated their knowledge of breast cancer (from 1-none to 10-extremely knowledgeable) with a median response of 3 (IQR: 1-4). Only 14% felt they knew any signs or symptoms of breast cancer. Encouragingly, 56% of women were fairly-to-very confident they would notice changes in their breasts, with 24% of women practicing self-breast examination and 21% reporting they had received a past breast exam. Overall, 74% said they would be somewhat-to-very likely to seek care if they noticed breast changes, with 96% noting severity of symptoms as a motivator. However, fear of losing a breast (40%) and fear of a poor diagnosis (38%) were most frequent barriers to care seeking. In assessing knowledge of risk factors, about 50% of women did not know any risk factors for breast cancer whereas 42% of women believed long term contraceptive use a risk factor. However, 37% and 35% of women did not think that family history or being older were risk factors, respectively.

Conclusions: The success of efforts to improve early diagnosis in a setting without population-based screening depends on women being aware of breast cancer signs and symptoms, risks, and ultimately seeking care for breast concerns. Fortunately, most women said they would seek care if they noticed a change in their breasts, but the low levels of cancer knowledge, symptoms, and common risk factors highlight the need for targeted community education and awareness campaigns.
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http://dx.doi.org/10.1186/s12889-020-09010-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296642PMC
June 2020

Mean platelet counts are relatively decreased with malaria but relatively increased with endemic Burkitt Lymphoma in Uganda, Tanzania, and Kenya.

Br J Haematol 2020 09 12;190(5):772-782. Epub 2020 May 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Platelet counts are decreased in Plasmodium falciparum malaria, which is aetiologically linked with endemic Burkitt lymphoma (eBL). However, the pattern of platelet counts in eBL cases is unknown. We studied platelet counts in 582 eBL cases and 2 248 controls enrolled in a case-control study in Uganda, Tanzania and Kenya (2010-2016). Mean platelet counts in controls or eBL cases with or without malaria-infection in controls versus eBLcases were compared using Student's t-test. Odds ratios (ORs) and two-sided 95% confidence intervals (95% CIs) were estimated using multiple logistic regression, controlling for age, sex, haemoglobin and white blood cell counts. Platelets were decreased with malaria infection in the controls [263 vs. 339 × 10 platelets/l, P < 0·0001; adjusted OR (aOR) = 3·42, 95% CI: 2·79-4·18] and eBL cases (314 vs. 367 × 10 platelets/l, P-value = 0·002; aOR = 2·36, 95% CI: 1·49-3·73). Unexpectedly, platelets were elevated in eBL cases versus  controls in overall analyses (mean: 353 vs. 307 × 10 platelets/l, P < 0·0001; aOR = 1·41; 95% CI: 1·12-1·77), and when restricted to malaria-positive (mean 314 vs. 263 × 10 platelets/l, P < 0·0001; OR = 2·26; 95% CI: 1·56-3·27) or malaria-negative (mean 367 vs. 339 × 10 platelets/l, P < 0·001; OR = 1·46; 95% CI: 1·17-1·83) subjects. Platelets were decreased with malaria infection in controls and eBL cases but elevated with eBL.
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http://dx.doi.org/10.1111/bjh.16700DOI Listing
September 2020

Using digital health to facilitate compliance with standardized pediatric cancer treatment guidelines in Tanzania: protocol for an early-stage effectiveness-implementation hybrid study.

BMC Cancer 2020 Mar 29;20(1):254. Epub 2020 Mar 29.

Department of Population Health Sciences, 215 Morris St, Durham, NC, 27701, USA.

Background: In high-income countries (HICs), increased rates of survival among pediatric cancer patients are achieved through the use of protocol-driven treatment. Compared to HICs, differences in infrastructure, supportive care, and human resources, make compliance with protocol-driven treatment challenging in low- and middle-income countries (LMICs). For successful implementation of protocol-driven treatment, treatment protocols must be resource-adapted for the LMIC context, and additional supportive tools must be developed to promote protocol compliance. In Tanzania, an LMIC where resource-adapted treatment protocols are available, digital health applications could promote protocol compliance through incorporation of systematic decision support algorithms, reminders and alerts related to patient visits, and up-to-date data for care coordination. However, evidence on the use of digital health applications in improving compliance with protocol-driven treatment for pediatric cancer is limited. This study protocol describes the development and evaluation of a digital health application, called mNavigator, to facilitate compliance with protocol-driven treatment for pediatric cancer in Tanzania.

Methods: mNavigator is a digital case management system that incorporates nationally-approved and resource-adapted treatment protocols for two pediatric cancers in Tanzania, Burkitt lymphoma and retinoblastoma. mNavigator is developed from an open-source digital health platform, called CommCare, and guided by the Consolidated Framework for Implementation Research. From July 2019-July 2020 at Bugando Medical Centre in Mwanza, Tanzania, all new pediatric cancer patients will be registered and managed using mNavigator as the new standard of care for patient intake and outcome assessment. Pediatric cancer patients with a clinical diagnosis of Burkitt lymphoma or retinoblastoma will be approached for participation in the study evaluating mNavigator. mNavigator users will document pre-treatment and treatment details for study participants using digital forms and checklists that facilitate compliance with protocol-driven treatment. Compliance with treatment protocols using mNavigator will be compared to historical compliance rates as the primary outcome. Throughout the implementation period, we will document factors that facilitate or inhibit mNavigator implementation.

Discussion: Study findings will inform implementation and scale up of mNavigator in tertiary pediatric cancer facilities in Tanzania, with the goal of facilitating protocol-driven treatment.

Trial Registration: The study protocol was registered in ClinicalTrials.gov (NCT03677128) on September 19, 2018.
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http://dx.doi.org/10.1186/s12885-020-6611-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104518PMC
March 2020

Evaluating the appropriateness of chemotherapy in a low-resource cancer centre in sub-Saharan Africa.

Cancer Med 2020 01 13;9(1):133-140. Epub 2019 Nov 13.

Oncology Pharmacy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Background: To evaluate the appropriateness of chemotherapy use at the Oncology Department of the Bugando Medical Centre of Mwanza, Tanzania.

Methods: The study was an observational prevalence-based study designed to evaluate a single-chemotherapy cycle during a defined time period for a cross-section of patients at varying stages of their clinical history. The sample included 103 consecutive subjects who were treated during January-March 2017 and had at least one previous cycle. Chemotherapy treatment omissions, cycle delays, and dose reductions and their causes were recorded using a standard form that included demographic, anthropometric, and clinical items. The data were analyzed descriptively.

Results: There were 59 males (57.3%) and 44 females (42.7%). Ninety-four patients were aged ≥18 years. Considering cancer type/site, there were 23 distinct groups of patients. The recorded number of drugs in the chemotherapy regimens varied between one and five. The median cycle number was three (range: 2-11). Sixty-eight (66.0%) patients were treated in a standard fashion. For the remaining, cycle delay and dose reduction were the most common cause for nonstandard treatment. Hematologic toxicity was responsible for the greater part of cycle delays, whereas dose reductions were accounted for by a larger spectrum of causes. Overall, toxicity explained 21/35 (60.0%) patients receiving nonstandard treatment. The distribution of toxic events was skewed toward grade 1 and grade 2.

Conclusions: The observed level of appropriateness of chemotherapy was encouraging. The proportion of patients experiencing severe toxic effects was lower than expected.
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http://dx.doi.org/10.1002/cam4.2672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943087PMC
January 2020

The whole-genome landscape of Burkitt lymphoma subtypes.

Blood 2019 11;134(19):1598-1607

Department of Immunology and.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
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http://dx.doi.org/10.1182/blood.2019001880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871305PMC
November 2019

Explaining the aggressiveness of breast cancer in sub-Saharan African patients.

J Clin Pathol 2019 10 13;72(10):723-724. Epub 2019 Aug 13.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

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http://dx.doi.org/10.1136/jclinpath-2019-206071DOI Listing
October 2019

Risk factors for Burkitt lymphoma in East African children and minors: A case-control study in malaria-endemic regions in Uganda, Tanzania and Kenya.

Int J Cancer 2020 02 20;146(4):953-969. Epub 2019 May 20.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub-Saharan African countries, however, few epidemiologic studies have been undertaken and none attempted enrolling cases from multiple countries. We therefore conducted a population-based case-control study of eBL in children aged 0-15 years old in six regions in Northern Uganda, Northern Tanzania and Western Kenya, enrolling 862 suspected cases and 2,934 population controls (response rates 98.5-100%), and processing ~40,000 vials of samples using standardized protocols. Risk factor questionnaires were administered, and malaria period prevalence was measured using rapid diagnostic tests (RDTs). A total of 80.9% of the recruited cases were diagnosed as eBL; 61.4% confirmed by histology. Associations with eBL risk were computed using logistic regression models adjusted for relevant confounders. Associations common in at least two countries were emphasized. eBL risk was decreased with higher maternal income and paternal education and elevated with history of inpatient malaria treatment >12 months before enrollment. Reporting malaria-attributed fever up to 6 months before enrollment and malaria-RDT positivity at enrollment were associated with decreased eBL risk. Conversely, reporting exposure to mass malaria suppression programs (e.g., indoor residual insecticide) was associated with elevated risk. HIV seropositivity was associated with elevated eBL risk, but the relative impact was small. The study shows that it is feasible to conduct networked, multisite population-based studies of eBL in Africa. eBL was inversely associated with socioeconomic status, positively associated with inpatient malaria treatment 12 months ago and with living in areas targeted for malaria suppression, which support a role of malaria in eBL.
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http://dx.doi.org/10.1002/ijc.32390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829037PMC
February 2020

Pediatric Cancer in Northern Tanzania: Evaluation of Diagnosis, Treatment, and Outcomes.

J Glob Oncol 2018 09 9;4:1-10. Epub 2017 Jun 9.

Kristin Schroeder, Anthony Saxton, Christina Chao, Daniel S. Wechsler, and Nelson Chao, Duke University, Durham, NC; Jessica McDade, Seattle Children's, Seattle, WA; Nestory Masalu and Beda Likonda, Bugando Medical Centre, Mwanza, Tanzania; and Colin Chao, Eastern Virginia Medical School, Norfolk, VA.

Purpose: The majority of new diagnoses of pediatric cancer are made in resource-poor countries, where survival rates range from 5% to 25% compared with 80% in high-resource countries. Multiple factors, including diagnostic and treatment capacities and complex socioeconomic factors, contribute to this variation. This study evaluated the available resources and outcomes for pediatric patients with cancer at the first oncology treatment center in northern Tanzania.

Methods: Qualitative interviews were completed from July to August 2015 to determine available staff, hospital, diagnostic, treatment, and supportive care resources. A retrospective review of hospital admissions and clinic visits from January 2010 to August 2014 was completed. A total of 298 patients were identified, and data from 182 patient files were included in this review.

Results: Diagnostic, treatment, and supportive capacities are limited for pediatric cancer care. The most common diagnoses were Burkitt lymphoma (n = 32), other non-Hodgkin lymphoma (n = 26), and Wilms tumor (n = 25). A total of 40% of patients (n = 72) abandoned care. There was a 20% 2-year event-free survival rate, which was significantly affected by patient age, method of diagnosis, and year of diagnosis.

Conclusion: To our knowledge, this is the first review of pediatric cancer outcomes in northern Tanzania. The study identified areas for future development to improve pediatric cancer outcomes, which included strengthening of training and diagnostic capacities, development of registries and research databases, and the need for additional research to reduce treatment abandonment.
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http://dx.doi.org/10.1200/JGO.2016.009027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180837PMC
September 2018

Qualitative Analysis of Palliative Care for Pediatric Patients With Cancer at Bugando Medical Center: An Evaluation of Barriers to Providing End-of-Life Care in a Resource-Limited Setting.

J Glob Oncol 2018 07;4:1-10

B. Emily Esmaili and Kearsley A. Stewart, Duke University; Kristin M. Schroeder, Duke University Medical Center, Durham, NC; and Nestory A. Masalu, Bugando Medical Center, Mwanza, Tanzania.

Purpose Palliative care remains an urgent, neglected need in the developing world. Global disparities in end-of-life care for children, such as those with advanced cancers, result from barriers that are complex and largely unstudied. This study describes these barriers at Bugando Medical Center, one of three consultant hospitals in Tanzania, to identify areas for palliative care development suitable to this context. Methods In-depth interviews were conducted with 20 caregivers of pediatric patients with cancer and 14 hospital staff involved in pediatric end-of-life care. This was combined with 1 month of participant observation through direct clinical care of terminally ill pediatric patients. Results Data from interviews as well as participant observation revealed several barriers to palliative care: financial, infrastructure, knowledge and cultural (including perceptions of pediatric pain), and communication challenges. Although this study focused on barriers, what also emerged were the unique advantages of end-of-life care in this setting, including community cohesiveness and strong faith background. Conclusion This study provides a unique but focused description of barriers to palliative care common in a low-resource setting, extending beyond resource needs. This multidisciplinary qualitative approach combined interviews with participant observation, providing a deeper understanding of the logistical and cultural challenges in this setting. This new understanding will inform the design of more effective-and more appropriate-palliative care policies for young patients with cancer in the developing world.
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http://dx.doi.org/10.1200/JGO.17.00047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223406PMC
July 2018

Dried Blood and Serum Spots As A Useful Tool for Sample Storage to Evaluate Cancer Biomarkers.

J Vis Exp 2018 06 11(136). Epub 2018 Jun 11.

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Blood sample quality is crucial to ensure accurate downstream analyses such as real-time PCR or ELISA. Correct storage of biological materials is the starting point to achieve reproducible and reliable results. All samples should be treated in the same way from blood collection to storage. Depending on the analyses to be performed, whole blood and serum samples should be stored at -20 °C or -80 °C until use. Blood/serum samples should also be aliquoted to avoid multiple freeze-thawing. Another important issue is the sample conditions during shipment from one laboratory to another. If dry ice is not available or the shipment takes longer than a few days, alternative approaches are needed. One option is to use filter paper for blood collection. Here, we propose a method for blood and serum sample collection that takes advantage of dried blood spots (DBS) and dried serum spots (DSS). We developed the procedure to extract DNA from DBS for the downstream evaluation of some single nucleotide polymorphisms (SNPs) by real time PCR. We also optimized an ELISA assay starting from proteins eluted from DSS. This method can be used with other ELISA assays or procedures evaluating proteins.
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http://dx.doi.org/10.3791/57113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101696PMC
June 2018

Are There Differences in Androgen Receptor Expression in Invasive Breast Cancer in African (Tanzanian) Population in Comparison With the Caucasian (Italian) Population?

Front Endocrinol (Lausanne) 2018 29;9:137. Epub 2018 Mar 29.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Androgen receptor (AR) has been shown to have prognostic implication on breast cancer (BC). Data on the biological features of African BCs are poor. We decided for the first time to compare AR expression of Tanzanian and Italian BC patients.

Patients And Methods: Of the 69 consecutive patients seen at the Bugando Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent resection of primary BC evaluable for estrogen receptor, progesterone receptor (PgR), and HER2 only 65 were evaluable for AR by immunohistochemistry. Histopathological assessment and biomolecular determinations were performed at the Cancer Institute of Romagna [Istituto Scientifico Romagnolo per lo studio e la cura dei tumori (IRST)-IRCCS, Meldola, Italy]. Caucasian BC patients were selected from an electronic database and matched (1:2 ratio) for year of diagnosis and age at diagnosis.

Results: The median age of patients at diagnosis was 51 (range 29-83) years for Tanzanian and 53 (range 26-86) years for Italian patients. Tanzanian patients harbored tumors with lower AR expression than Italian patients according to the median percentage of immunopositive tumor cells (30% versus 80%,  < 0.0001) and staining intensity ( = 0.0003). The proportion of AR negative patients was likewise higher among Tanzanian patients as regards both ≥1% and ≥10% cutoffs. AR-positive BCs were higher in luminal A and B tumors and decreased in triple-negative (TN) and HER2-enriched tumors in Tanzanian population.

Conclusion: AR loss could represent an unfavorable prognostic marker in the African population. The high frequency of TN tumors with high AR expression could open new perspectives of therapy for population in this low income country.
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http://dx.doi.org/10.3389/fendo.2018.00137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885470PMC
March 2018

Setting up a community-based cervical screening service in a low-income country: a pilot study from north-western Tanzania.

Int J Public Health 2017 Sep 19;62(7):755-762. Epub 2017 Apr 19.

Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Objectives: To report the results of a pilot study for a service for cervical cancer screening and diagnosis in north-western Tanzania.

Methods: The pilot study was launched in 2012 after a community-level information campaign. Women aged 15-64 years were encouraged to attend the district health centres. Attendees were offered a conventional Pap smear and a visual inspection of the cervix with acetic acid (VIA).

Results: The first 2500 women were evaluated. A total of 164 women (detection rate 70.0/1000) were diagnosed with high-grade cervical intraepithelial neoplasia and invasive cervical cancer. The performance of VIA was comparable to that of Pap smear. The district of residence, a history of untreated sexually transmitted disease, an HIV-negative status (inverse association), and parity were independently associated with the detected prevalence of disease. The probability of invasive versus preinvasive disease was lower in HIV-positive women and in women practicing breast self-examination.

Conclusions: The diagnostic procedure had an acceptable level of quality. Factors associated with the detected prevalence of disease will allow for a more targeted promotion of the service. Cervical screening should be coordinated with sexually transmitted disease and HIV infection control activities.
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http://dx.doi.org/10.1007/s00038-017-0971-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585293PMC
September 2017

Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway.

Oncotarget 2017 Feb;8(8):13142-13156

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

As total vitamin D levels are often lower in black than in white Americans, the former are frequently classified as vitamin D-deficient. To fully understand African vitamin D (25(OH)D) status, other factors should be considered, e.g. vitamin D blood carrier, vitamin D-binding protein (DBP), vitamin D receptor (VDR) and DBP polymorphisms. A prospective study on an indigenous black Tanzanian and a Caucasian Italian population was performed on 50 healthy donors from both populations and 35 Caucasian and 18 African breast cancer patients. 25(OH)D and DBP serum levels were analyzed by ELISA. A1012G, Cdx2 and Fok1 VDR polymorphisms and DBP polymorphisms rs4588 and rs7041 were genotyped by real-time PCR. Vitamin D and DBP levels were lower in healthy African donors than in Caucasians. Africans had a significantly higher frequency of AA and CC for Cdx2 and Fok1 polymorphisms, respectively. These allelic variants were related to a higher transcription of VDR gene and a higher activity of VDR receptor. With regard to polymorphism distribution, Africans showed innate higher levels and activity of VDR. We conclude that a strengthening of the vitamin D pathway could have a protective role against the development of breast cancer in the African population.
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http://dx.doi.org/10.18632/oncotarget.14482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355083PMC
February 2017

The Mwanza Cancer Project.

Lancet Oncol 2016 Feb;17(2):146-148

Medical Oncology Unit, Bugando Medical Centre (BMC) Mwanza, Tanzania, Africa.

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http://dx.doi.org/10.1016/S1470-2045(16)00012-7DOI Listing
February 2016

Head and neck cancers: a clinico-pathological profile and management challenges in a resource-limited setting.

BMC Res Notes 2015 Dec 12;8:772. Epub 2015 Dec 12.

Department of Surgery, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.

Background: Head and neck cancer (HNC) is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding head and neck cancers in Tanzania, and Bugando Medical Centre in particular. This study describes the clinicopathological profile of HNC in our local setting and highlights the challenges in the management of this disease.

Methods: This was a retrospective study of histopathologically confirmed cases of head and neck cancers treated at Bugando Medical Center between January 2009 and December 2013.

Results: A total of 346 patients (M:F = 2.1:1) were studied representing 9.5 % of all malignancies. The median age of patients was 42 years. Cigarette smoking (76.6 %) and heavy alcohol consumption (69.9 %) were the most frequently identified risk factors for head and neck cancer. The majority of patients (95.9 %) presented late with advanced stages. Twenty-five (7.2 %) patients were HIV positive with a median CD4+ count of 244 cells/μl. The oral cavity (37.3 %) was the most frequent anatomical site affected. The most common histopathological type was carcinomas (59.6 %) of which 75.7 % were squamous cell carcinoma. A total of 196 (56.6 %) patients underwent surgical procedures for HNC. Radiotherapy and chemotherapy was reported in 9.5 and 16.8 % of patients, respectively. Only 2 (0.6 %) patients received chemo-radiation therapy. The mortality rate was 24.4 %. The overall 5-year survival rate (5-YSR) was 20.6 %. The predictors of overall 5-YSR were age of patient at diagnosis, stage of disease, extent of lymph node involvement, HIV seropositivity and CD4+ count <200 cells/μl (P < 0.001). Local recurrence was reported in 22 (23.4 %) patients and this was significantly associated with positive resection margins, stage of the tumor and presence of metastasis at diagnosis and non-adherence to adjuvant therapy (P < 0.001).

Conclusion: Head and neck cancers are not uncommon at Bugando Medical Centre and show a trend towards a relative young age at diagnosis and the majority of patients present late with advanced stage cancer. Therefore, public enlightenment, early diagnosis, and effective cost-effective treatment and follow-up are urgently needed to improve outcomes of these patients in our environment.
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http://dx.doi.org/10.1186/s13104-015-1773-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676813PMC
December 2015

Kaposi's sarcoma: a 10-year experience with 248 patients at a single tertiary care hospital in Tanzania.

BMC Res Notes 2015 Sep 15;8:440. Epub 2015 Sep 15.

Department of Internal Medicine, Catholic University of Health and Allied Science-Bugando, Mwanza, Tanzania.

Background: Kaposi's Sarcoma is the most common sarcoma and second most prevalent cancer seen in Tanzania. Little is known about Kaposi's sarcoma in our setting as there is paucity of recent published data regarding this condition. This study describes the clinicopathological pattern and treatment outcome of Kaposi's sarcoma at Bugando Medical Centre, a tertiary care hospital in northwestern Tanzania.

Methods: This was a prospective study of histologically confirmed Kaposi's sarcoma that was conducted at Bugando Medical Center between July 2004 and June 2014.

Results: A total of 248 patients (M:F = 1.4:1) representing 2.4% of all malignancies during the study period were enrolled into the study. The median age at presentation was 36 years. Females were younger than males (p = 0.04). Out of 248 patients, 122 (49.2%) were HIV positive. Of these, 46 (37.7%) were males and 76 (62.3%) females. AIDS-related Kaposi's sarcoma were younger than HIV negative Kaposi's sarcoma patients (p = 0.011). Median duration of symptoms was 6 months. Kaposi's sarcoma was the AIDS defining disease in 82 (67.2%) patients while in the remaining 40 (32.8%) it was diagnosed between 1 and 14 months after the initial diagnosis of AIDS. The lower limb was most frequently involved site in 28.9% of patient. Females had more disseminated lesions compared with more localized lesions in the males (p = 0.001). The treatment modalities in this study included chemotherapy, radiotherapy, surgery and highly active antiretroviral therapy. Overall 126 (53.4%) patients had significant improvement in quality of life at the end of 1 year follow up. Treatment related complication and mortality rates were 25.8 and 24.2% respectively. Poor ACTG stage, CD4+ count <200 cells/µl, associated co-morbid illness, disseminated disease and poor adherent to chemotherapy were the significant independent factors associated with deaths (p < 0.001). Patient's follow-up was generally poor and data on long-term survivals were not available as more than two-thirds of patients were lost to follow up.

Conclusion: Kaposi's sarcoma is the most common malignant vascular tumor and HIV/AIDS- related cancer in our region. There is an urgent need to develop health education programmes to enhance the understanding of this disease and how it spreads, particularly among the younger generation.
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http://dx.doi.org/10.1186/s13104-015-1348-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439227PMC
September 2015

Ten-year surgical experiences with penile cancer at a tertiary care hospital in northwestern Tanzania: a retrospective study of 236 patients.

World J Surg Oncol 2015 Feb 22;13:71. Epub 2015 Feb 22.

Department of Urology, Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.

Background: Penile cancer is an uncommon malignancy in developed countries, but the incidence is as high as 10% to 20% of all male cancers in some developing countries. There is a paucity of published data on this subject in our setting. This study describes the clinicopathological presentation and treatment outcome of this condition in our environment, and highlights challenges associated with the care of these patients and proffers solutions for improved outcome.

Methods: This was a retrospective study of histologically confirmed cases of penile cancer seen at Bugando Medical Centre between January 2004 and December 2013.

Results: There were 236 penile cancer patients representing 2.2% of all male malignancies during the study period. The median age was 47 years with a modal age group of 41 to 50 years. Of the 236 patients, 147 (62.3%) had severe phimosis. The majority of patients (89.8%) were uncircumcised. A history of human papilloma virus (HPV) was reported in 12 (5.1%) cases. One hundred eighty-two (77.1%) patients reported history of cigarette smoking. Seven (6.7%) patients were human immunodeficiency virus (HIV) positive. The majority of the patients (68.6%) presented with Jackson's stages III and IV. Squamous cell carcinoma was the most common histopathological type (99.2%). Lymph node metastasis was recorded in 65.3% of cases, and it was significantly associated with the tumor size, histopathological subtype, histopathological grade, lympho-vascular invasion, positive resection margins, and urethral involvement (P < 0.001). Distant metastasis accounted for 4.2% of cases. The majority of patients (63.1%) underwent partial penectomy. Chemotherapy and radiotherapy were given in 14 (5.9%) and 12 (5.1%) patients, respectively. Complication and mortality rates were 22.0% and 4.2%, respectively. HIV positivity, histopathological stage and grade of the tumor, and presence of metastases at the time of diagnosis were the main predictors of death (P < 0.001). The median length of hospitalization was 14 days. Local recurrence was reported in 12 (5.3%) patients. Data on long-term survivals were not available as the majority of patients were lost to follow-up.

Conclusions: Penile cancer is not rare in our environment. The majority of patients present late with advanced stage of the disease. Early detection of primary cancer at an early stage may improve the prognosis.
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http://dx.doi.org/10.1186/s12957-015-0482-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341227PMC
February 2015

Burkitt lymphoma research in East Africa: highlights from the 9(th) African organization for research and training in cancer conference held in Durban, South Africa in 2013.

Infect Agent Cancer 2014 11;9:32. Epub 2014 Sep 11.

National Institutes of Health/NCI/DCEG, 9609 Medical Center Dr, Rm. 6E118 MSC 9704, Bethesda, MD 20892-9704, USA.

A one-day workshop on Burkitt lymphoma (BL) was held at the 9(th) African Organization for Research and Training in Cancer (AORTIC) conference in 2013 in Durban, South Africa. The workshop featured 15 plenary talks by delegates representing 13 institutions that either fund or implement research on BL targeting AORTIC delegates primarily interested in pediatric oncology. The main outcomes of the meeting were improved sharing of knowledge and experience about ongoing epidemiologic BL research, BL treatment in different settings, the role of cancer registries in cancer research, and opportunities for African scientists to publish in scientific journals. The idea of forming a consortium of BL to improve coordination, information sharing, accelerate discovery, dissemination, and translation of knowledge and to build capacity, while reducing redundant efforts was discussed. Here, we summarize the presentations and discussions from the workshop.
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http://dx.doi.org/10.1186/1750-9378-9-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163050PMC
February 2015

Hepatocellular carcinoma: clinicopathological profile and challenges of management in a resource-limited setting.

World J Surg Oncol 2014 Aug 2;12:246. Epub 2014 Aug 2.

Department of Surgery, Catholic University of Health and Allied Sciences- Bugando, Bugando, P,O, Box 1464, Mwanza, Tanzania.

Background: Hepatocellular carcinoma is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding hepatocellular carcinoma in Tanzania, and the study area in particular. This study describes the clinicopathological profile of hepatocellular carcinoma in our local setting and highlights the challenging problems in the management of this disease.

Methods: This was a retrospective study of histopathologically confirmed cases of hepatocellular carcinoma seen at Bugando Medical Center between March 2009 and February 2013.

Results: A total of 142 patients (M: F = 2.2: 1) were studied representing 4.6% of all malignancies. The median age of patients was 45 years. Hepatitis B virus infection (66.2%) and heavy alcohol consumption (60.6%) were the most frequently identified risk factors for hepatocellular carcinoma. The majority of patients (88.0%) presented late with advanced stages. HBsAg was positive in 66.2% of the patients and Hepatitis C Virus antibody in 16.9%. Thirteen (9.2%) patients tested positive for HIV infection. Most patients (52.8%) had both right and left lobe involvement. The trabecular pattern (47.9%) was the most frequent histopathological type. None of patients had curative therapy because of the advanced nature of the disease. Coagulopathy (45.7%) was the most common complications. The overall mortality rate was 46.5% and it was significantly associated with comorbidity, HIV positivity, CD4+ count <200 cells/μl, high histological grade, advanced stage of the tumor, presence of distant metastases at the time of diagnosis, and associated complications (P < 0.001). The overall median duration of hospital stay was 14 days. The majority of patients (71.1%) were lost to follow-up at the end of the follow-up period.

Conclusions: Hepatocellular carcinoma patients in this region are relatively young at diagnosis and the majority of them present late with an advanced stage and high rate of distant metastasis. Lack of awareness of the disease, poor accessibility to healthcare facilities, and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment, and proper follow-up to improve treatment outcome.
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http://dx.doi.org/10.1186/1477-7819-12-246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121298PMC
August 2014

Triple negative breast cancer in a poor resource setting in North-Western Tanzania: a preliminary study of 52 patients.

BMC Res Notes 2014 Jun 26;7:399. Epub 2014 Jun 26.

Pathology Department, Catholic University of Health and Allied Sciences-Bugando, Box 1464, Mwanza, Tanzania.

Background: Breast cancer is the second leading cancer worldwide. In Tanzania, though it ranks as the second leading cancer in women after cervical cancer, hormonal receptor status is not carried out routinely in patients. Adjuvant hormonal therapy is given without prior knowledge of hormonal receptors status and patients can incur unnecessary costs and side effects. This study was performed to investigate the expression of hormonal receptors, epidermal growth factor receptors (HER-2) and proliferation index of the breast cancer by Ki-67 in a few selected patients with breast cancer at referral hospital in North-Western Tanzania. The study classified breast cancer subtypes based on hormonal receptors status and the expression of epidermal growth factor receptors.

Results: A total of 52 cases of breast cancer were investigated. Patients' mean age at diagnosis was 49 years. The majority of the tumors was invasive ductal carcinoma 47 (90.4%) and 40 (76.9%) were of histological grade III. Thirty-eight (73.1%) of the patient had lymph node metastasis at the time of diagnosis and 36 (69.2%) were at clinical stage III. Only 3 (5.8%) patients were in clinical stage I. There was a tendency of a low level of expression of the receptors, whereby Estrogen Receptor (ER) positive tumors were 17 (32.7%), progesterone receptor (PR) positive tumors were 22 (42.3%), and HER-2 positive tumors were 12 (23.1%). Triple negative tumors constituted 20 (38.4%) of the patients. Most of the tumors (75%) showed high proliferation by Ki-67. Lymph node metastasis was more common in Triple Negative and HER enriched tumors.

Conclusion: This study showed a tendency for a low level of expression of hormonal receptors. There was a significant proportion of Triple Negative breast cancers. Routine testing for hormonal receptors in breast cancer is recommended before the initiation of adjuvant hormonal therapy.
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http://dx.doi.org/10.1186/1756-0500-7-399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081017PMC
June 2014

Prevalence and predictors of Cervical Intraepithelial Neoplasia among HIV infected women at Bugando Medical Centre, Mwanza-Tanzania.

Infect Agent Cancer 2013 Nov 15;8(1):45. Epub 2013 Nov 15.

Department of Oncology, Bugando Medical Centre, Box 1370, Mwanza, Tanzania.

Introduction: Cancer of the cervix rank the second most common cause of cancer related deaths among women in Sub-Saharan Africa. It is estimated that 529, 409 new cases are diagnosed annually with a mortality rate approaching 274,883 per year. Cervical Intraepithelial Neoplasia (CIN) precedes almost all cervical cancers. The incidence rate of CIN among HIV infected women is five times higher as compared to the rate in HIV negative women. The screening for cervical dysplasia and an appropriate management in women with CIN are effective methods for preventing cervical cancer. This study was done to determine the prevalence and predictors of CIN among a HIV infected women attending Care and Treatment centre (CTC) at Bugando Medical Centre (BMC).

Methods: A cross sectional survey was undertaken among HIV infected women aged 18 years and above attending at BMC CTC clinic between February and March 2013. Visual Inspection with Acetic acid (VIA) was used as the screening method for detection of CIN. Socio-demographic, reproductive and clinical information was obtained from participants and the blood was collected for CD4 lymphocyte count. Cervical punch biopsy for histological examination was performed for those who had VIA positive test. Data were entered and analyzed using STATA Version 12.0 soft ware.

Results: A total number of 95 (26.8%) participants had positive VIA test among three hundred and fifty-five (355) HIV infected women. Histology results showed; 4(4.2%) were normal, 26 (27.4%) had an inflammatory lesion, 58(61.1%) had CIN and 7(7.3%) had invasive cervical cancer. CIN was found to be associated with a history of multiple sexual partners (P<0.001), a history of genital warts (P<0.001), and a history of STI (P = 0.010).

Conclusion: The Cervical Intraepithelial Neoplasia is a problem among HIV infected women. A history of multiple sexual partners, a history of genital warts, a history STI and a low baseline CD4 T lymphocyte were significant predictors for CIN. Screening for Cervical Intraepithelial Neoplasia is recommended for all women with HIV.
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http://dx.doi.org/10.1186/1750-9378-8-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833176PMC
November 2013

Triple assessment as a preoperative diagnostic tool for breast cancer at Bugando Medical Centre in northwestern Tanzania.

Tanzan J Health Res 2013 Oct;15(4):223-9

Department of Surgery, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.

The triple assessment in the pre-operative evaluation of breast cancer has been practiced in some hospitals in Tanzania. However, its validity and reliability has not been evaluated in any hospital in the country including the study area. This cross-sectional study was conducted at Bugando Medical Centre in northwestern Tanzania to determine the validity, reliability and applicability of triple assessment as an alternative to conventional open biopsy in the pre-operative diagnosis of breast cancer. A total of 212 female patients aged 35 years and above were studied. All patients underwent clinical evaluation, mammography and fine needle aspiration cytology. Histopathology was done to confirm the diagnosis. One hundred and twenty (56.6%) patients with a median age of 36 years had benign lesions and the remaining ninety-two (43.4%) with a median age of 47 years had breast cancer (P = 0.002). With triple assessment, 92 patients were diagnostic for malignancy and 120 benign, respectively confirmed by histopathology. The Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value and Accuracy were 100.0%. There were no false positive or false negative results. The Kappa statistic for the combination was 1.0 implying excellent agreement with histopathology. The majority of patients (59.9%) underwent triple assessment on the same day with results being available to the patient within 24 to 72 hours. The triple assessment is an accurate and quick method for the evaluation of breast cancer and can be applied as a safe alternative for open biopsy when it is concordant.
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http://dx.doi.org/10.4314/thrb.v15i4.3DOI Listing
October 2013

Dried blood spot sampling for detection of monoclonal immunoglobulin gene rearrangement.

Leuk Res 2013 Oct 13;37(10):1265-70. Epub 2013 Aug 13.

Department of Surgery, Oncology and Gastroenterology, Section of Immunology and Oncology, AIDS Reference Center, University of Padova, Padova, Italy.

Molecular methods are important tools for diagnosis and monitoring of many lymphoproliferative disorders. The reliability of lymphoma diagnoses is strikingly different between developed and developing countries, partly due to lack of access to these advanced molecular analyses. To overcome these problems, we propose a new application of dried blood spots (DBS) for detecting clonal B-cell populations in peripheral blood (PB). We ensured that the DBS contained sufficient lymphocytes to perform a PCR-based clonality assay without producing false positives. Using the Namalwa B-cell line, we established that the assay is sensitive enough to detect 200 clonal cells in the analyzed sample. Very similar clonal results were obtained between DNA from DBS and fresh whole blood from patients with B-cell chronic lymphocytic leukemia. B-cell clonality can also be detected in DBS from African children with EBV-associated diseases. This is the first study demonstrating that clonality testing can be performed on DBS samples, thus improving the diagnostic and monitoring options for lymphoproliferative diseases in resource-limited settings.
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http://dx.doi.org/10.1016/j.leukres.2013.08.003DOI Listing
October 2013

Biofunctional characteristics of in situ and invasive breast carcinoma.

Cell Oncol (Dordr) 2013 Jul 27;36(4):303-10. Epub 2013 Jun 27.

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, FC, Italy.

Purpose: The increasing use of breast-conserving surgery makes it essential to identify biofunctional profiles responsible for the progression of in situ to invasive carcinomas to facilitate the detection of lesions that are most likely to relapse or progress and, thus, to be able to offer patients tailored treatment options. Our objective was to analyse and compare biofunctional profiles in ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC). We also aimed to identify markers in tumor and normal surrounding tissues that may be predictive of locoregional recurrence in patients with DCIS.

Methods: Biofunctional parameters including mitotic activity, estrogen receptor, progesterone receptor, microvessel density (MVD), c-kit and p27 expression were evaluated in 829 in situ and invasive carcinomas. The impact of the biomarker profiles of DCIS, IDC and normal surrounding tissues on loco-regional recurrence was analyzed.

Results: A progressive increase in cell proliferation and a concomitant decrease in steroid hormone receptor-positive lesions was observed during the transition from in situ to invasive carcinomas, as also within each subgroup as grade increased. Conversely, p27 expression and MVD dramatically decreased during the transition from in situ to invasive carcinomas. Finally, we found that a low c-kit expression was indicative of IDC relapse.

Conclusions: Cell proliferation, hormonal and differentiation characteristics differed in DCIS with respect to IDC, and the main variation in the transition between the two histologic lesions was the decrease in p27 expression and MVD.
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http://dx.doi.org/10.1007/s13402-013-0135-7DOI Listing
July 2013