Erratum: Prostate cancer clinical characteristics and outcomes in Central Sudan.

[This corrects the article on p. 1 in vol. 14.].

Prostate cancer clinical characteristics and outcomes in Central Sudan.

BACKGROUND: Prostate cancer is the most common cancer among Sudanese men and most patients present at a late stage. Although the incidence of prostate cancer in Sudan is low compared to other African countries, studies on prostate cancer in Sudan are limited. This study addresses the clinical characteristics and outcomes of prostate cancer in Central Sudan and its prognostic factors. METHODOLOGY: This study was conducted prospectively at the Gezira Hospital for Renal Disease and Surgery and at the National Cancer Institute at the University of Gezira, Sudan, for an 11-year period. RESULTS: During the study period, 543 patients participated in the study. Each one underwent a clinical examination, digital rectal examination and radiological staging using magnetic resonance imaging or computed tomography and provided blood samples for prostate-specific antigen (PSA) testing. The mean (SD) age of patients was 72.6 (9.9) years. At diagnosis, the majority of patients experienced lower urinary tract symptoms (LUTS; 54%), bladder outlet obstructions (OU) without (18%) or with urine retention (14%), PSA median was 100 ng/mL and the mean was 269 ng/mL, locally advanced disease (45%) or distant metastasis (46%). The age-adjusted hazard ratio (HR) of mortality was twofold, comparing patients presented with OU to patients with LUTS. Patients diagnosed with locally advanced and castration resistance prostate cancer had five times the HR compared to patients diagnosed with organ-confined prostate. On the contrary, the HR increased sevenfold for patients with distant metastasis. Gleason score did not show a significant association with survival (p = 0.249). Similarly, there was no apparent dose-response association between the PSA levels at diagnosis (p = 0.460). CONCLUSION: The findings suggest that Sudanese men who are living in Central Sudan present at diagnosis with large tumours at late stages, and high PSA levels and Gleason scores. Improving awareness and building up the treatment capacity are key to achieving better outcomes.

Choosing Wisely Africa: Ten Low-Value or Harmful Practices That Should Be Avoided in Cancer Care.

PURPOSE: Choosing Wisely Africa (CWA) builds on Choosing Wisely (CW) in the United States, Canada, and India and aims to identify low-value, unnecessary, or harmful cancer practices that are frequently used on the African continent. The aim of this work was to use physicians and patient advocates to identify a short list of low-value practices that are frequently used in African low- and middle-income countries. METHODS: The CWA Task Force was convened by the African Organization for Research and Training in Cancer and included representatives from surgical, medical, and radiation oncology, the private and public sectors, and patient advocacy groups. Consensus was built through a modified Delphi process, shortening a long list of practices to a short list, and then to a final list. A voting threshold of ≥ 60% was used to include an individual practice on the short list. A consensus was reached after a series of teleconferences and voting processes. RESULTS: Of the 10 practices on the final list, one is a new suggestion and 9 are revisions or adaptations of practices from previous CW campaign lists. One item relates to palliative care, 8 concern treatment, and one relates to surveillance. CONCLUSION: The CWA initiative has identified 10 low-value, common interventions in Africa's cancer practice. The success of this campaign will be measured by how the recommendations are implemented across sub-Saharan Africa and whether this improves the delivery of high-quality cancer care.

LXR/RXR pathway signaling associated with triple-negative breast cancer in African American women.

BACKGROUND: Triple-negative breast cancer (TNBC) is more prevalent in African and African American (AA) women compared to European American (EA) women. African and AA women diagnosed with TNBC experience high frequencies of metastases and less favorable outcomes. Emerging evidence indicates that this disparity may in fact be the result of the uniquely aggressive biology of African and AA disease. PURPOSE: To understand the reasons for TNBC in AA aggressive biology, we designed the present study to examine the proteomic profiles of TNBC and luminal A (LA) breast cancer within and across patients' racial demographic groups in order to identify proteins or molecular pathways altered in TNBC that offer some explanation for its aggressiveness and potential targets for treatment. MATERIALS AND METHODS: Proteomic profiles of TNBC, LA tumors, and their adjacent normal tissues from AA and EA women were obtained using 2-dimensional gel electrophoresis and bioinformatics, and differentially expressed proteins were validated by Western blot and immunohistochemistry. Our data showed that a number of proteins have significantly altered in expression in LA tumors compared to TNBC, both within and across patients' racial demographic groups. The differentially overexpressed proteins in TNBC (compared to LA) of AA samples were distinct from those in TNBC (compared to LA) of EA women samples. Among the signaling pathways altered in AA TNBC compared to EA TNBC are innate immune signaling, calpain protease, and pyrimidine de novo synthesis pathways. Furthermore, liver LXR/RXR signaling pathway was altered between LA and TNBC in AA women and may be due to the deficiency of the CYP7B1 enzyme responsible for cholesterol degradation. CONCLUSION: These findings suggest that TNBC in AA women enriched in signaling pathways that are different from TNBC in EA women. Our study draws a link between LXR/RXR expression, cholesterol, obesity, and the TNBC in AA women.

Incidence and survival rates of ovarian cancer in low-income women in Sudan.

Ovarian cancer is the second most common gynecological cancer worldwide. Little is known about the disease in Sudan. The objective of the present study was to evaluate the incidence rate, age and stage at diagnosis, and median survival time of patients presenting at the National Cancer Institute-University of Gezira (NCI-UG), Sudan. Data were collected in a prospective study of women with ovarian cancer over a period of eleven years of follow-up (between 2000 and 2011). Descriptive statistics were used to summarize the distribution of the demographics of the sample. The direct method was used to compute the age-standardized rate (ASR) using data from the 1966 and 2000 World Standard Populations (WSPs). The Kaplan-Meier method was used to estimate survival functions and the median survival time. Log-rank tests were used to statistically compare between the survival functions. There were steady increases in ovarian cancer incidence rates between 2000 and 2009, with a slight decline noted in 2010 and 2011. The patients' age range was 9-90. The age-specific incidence rate increased greatly in women aged 55 years or older. The majority of the patients had stage III or IV disease. The annual ASR using WSPs 1966 and 2000 as standard populations were 3.3 and 3.7 per 100,000 women, respectively. The median survival time was 31 months (95% confidence interval, 19-43). The 5-year cumulative survival rate was 38%. In Sudan, ovarian cancer affects postmenopausal women, akin to what is reported in the developed world with high incidence rates. Presenting with advanced stage disease is the predominant factor that results in a short survival time for women.

Part I: cancer in Sudan­burden, distribution, and trends breast, gynecological, and prostate cancers.

Despite the growing burden of cancer worldwide, it continues to receive low priority in Africa, across the continent and specifically in Sudan. This is due to political unrest, limited health resources, and other pressing public health issues such as infectious diseases. Lack of awareness about the magnitude of the current and future cancer burden among policy makers play a major role as well. Although, the real scope of cancer in Sudan is not known, the reported cases have increased from 303 in 1967-6303 in 2010. According to Globocan estimates, the top most common cancers in both sexes are breast, non-Hodgkin lymphoma, leukemia, esophagus, and colorectum. This review is the first of four papers that focuses on cancer, its distribution and trend as well as the risk factors most common in Sudan. It is expected that cancer will increase in Sudan as a result of migration of people from rural areas to urban cities in the pursuit of a better standard of living, which has resulted in lifestyle and behavioral changes that include tobacco chewing and smoking, unhealthy dieting, and a lack of physical activity. These changes are further exacerbated by the aging population and have made the country vulnerable to many diseases including cancer. These reviews are meant to provide a better understanding and knowledge required to plan appropriate cancer-control and prevention strategies in the country.

BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan.

Premenopausal breast cancer (BC) is one of the most common cancers of women in rural Africa and part of the disease load may be related to hereditary predisposition, including mutations in the BRCA1 gene. However, the BRCA1 mutations associated with BC in Africa are scarcely characterized. We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic variation and frequency of unique or rare mutations of uncertain clinical relevance pose significant challenges to BRCA1 testing in Sudan, as it might happen in other low-resource rural African contexts.

Breast-cancer screening with trained volunteers in a rural area of Sudan: a pilot study.

BACKGROUND: Breast cancer has a low cure rate in low-income and middle-income countries because patients often present with late-stage disease that has metastasised to other organs. We assessed whether the implementation of a cancer awareness and breast examination programme that uses local, volunteer women could increase the early detection of breast cancer in a rural area of sub-Saharan Africa. METHODS: We did this pilot study in two counties in Gezira State, Sudan. We chose Keremet (56 villages) as the experimental county and Abugota (79 villages) as the control county. Female volunteers from villages in Keremet were trained in the detection of breast abnormalities. When trained, volunteers visited households in their village and screened women aged 18 years or older for breast abnormalities, referring women with suspected breast cancer for medical diagnosis and, if necessary, treatment at the district hospital. We also ran a cancer awareness programme for both men and women in study villages. Villages in the control population received no intervention. This study is ongoing. FINDINGS: Between Jan 1, 2010, and Oct 10, 2012, 10 309 (70%) of 14 788 women in Keremet were screened. 138 women were identified as having breast abnormalities and were referred to the district hospital for diagnosis and treatment. 20 of these women did not report to the hospital. Of the 118 women who did report, 101 were diagnosed with benign lesions, eight with carcinoma in situ, and nine had malignant disease. After treatment, 12 of the 17 women with either carcinoma in situ or malignant disease (four had early breast cancer and eight had ductal carcinoma in situ) were disease-free and had a good prognosis. In the control villages, only four women reported to the centre: one was found to have a benign lesion while three were diagnosed with advanced disease. INTERPRETATION: Our findings show that a screening programme using local volunteers can increase the detection of breast cancer in asymptomatic women in low-income rural communities. These findings can inform policy-makers' decisions in the design of cancer control programmes in Sudan and other similar areas in sub-Saharan Africa. FUNDING: Sudan National Cancer Institute.

Clinical presentation and outcome of retinoblastoma among children treated at the National Cancer Institute (NCI) in Gezira, Sudan: a single Institution experience.

BACKGROUND: Retinoblastoma (RB) is a rare and unique cancer that affects the eyes of very young children. There are few reports on RB in Sudan. MATERIALS AND METHODS: We performed a retrospective study of data from patients diagnosed with retinoblastoma between January 1999 and December 2009 at the National Cancer Institute in Gezira (NCI-Gezira). RESULTS: Of the 519 cases of childhood cancer treated at NCI-Gezira during the study period, 25 (4.8%) were retinoblastoma. Of these 25 patients with retinoblastoma, there were 13 boys and 19 cases were unilateral. The median age at diagnosis was 36 months (range, 8-60 months). The disease was localized in 9 patients, regional in 5 patients, and metastatic in 11 patients. The most frequent symptoms were enlarged eye (n = 14) and leukocoria (n = 8). Nine patients (36%) have been lost to follow-up; 9 were alive at last follow-up (7 in remission, 2 progressed); and 7 have died (5 from disease and 2 from unrelated causes). Twenty-two eyes were enucleated in 16 patients (6 bilateral and 10 unilateral). Pathologic examination of the enucleated eyes could only be completed in 11 patients. Diagnostic imaging in the form of computerized tomography scans or ultrasonography of the brain and orbit was done for 10 patients (40%). CONCLUSIONS: Although these findings are not surprising, and similar to reports from other developing countries, we hope our work will provide a foundation for strategies to improve outcome for retinoblastoma in our center such as proper training, public awareness, team approach, and twinning.

Breast cancer burden in central Sudan.

Breast cancer is a worldwide disease resulting in many deaths. Although breast cancer incidence is lower in Sub-Saharan African countries than in developed countries, African women are more likely than women in the developed world to be diagnosed at later stages of the disease and, thus, are more likely to die from it. This is due to the lack of awareness by women, accessibility to screening methods, and availability of African-based research findings that would influence decision making at the governmental level. This descriptive study was undertaken to shed light on the type, stage and age distribution of breast cancer at diagnosis in women living in central Sudan encompassing al-Gezira, Blue Nile, White Nile, and Sennar States. Cases comprised 1255 women from central Sudan diagnosed with breast cancer and referred to and treated at Institute of Nuclear Medicine, Molecular Biology, and Oncology, from January 1999 to December 2006. Data revealed that 74% of the women were <50 years old or premenopausal. Invasive ductal carcinoma was the most common pathology (82%) and women presenting with stage III or higher tumors that had already metastasized, while ductal carcinoma in situ was the least prevalent (0.5%) finding. Estrogen and progesterone receptors expression were performed on a limited number of samples and the overwhelming majority of cases were observed to be negative for estrogen and progesterone receptors expression.

Childhood cancer in Sudan: 1999-2007.

There is paucity of information on childhood cancer from Sudan with the last studies published more than 20 years ago. This study aims to provide a current picture of childhood cancer in Sudan. Data was obtained from the hospital registry for the period May 1999 to June 2007 on all paediatric patients presenting to the Institute of Nuclear Medicine and Oncology, University of Gezira, Wad Madani, Sudan. There were 322 children with cancer during this time period with a male:female ratio of 1.6:1. Lymphomas (111, 35%), leukaemia (83, 26%) and Wilms' tumour (43, 13%) were the three most common groups of tumours. Thirty percent of all lymphomas were Burkitt's lymphoma; 3.4% of all childhood cancer cases were nasopharyngeal carcinomas.

Histopathological patterns of nasopharyngeal carcinoma in Sudan.

OBJECTIVE: To study the histological patterns of nasopharyngeal carcinoma NPC in Sudanese patients and to compare them with the internationally published series. METHODS: A retrospective review for records of NPC patients treated in the Institute of Nuclear Medicine, Molecular Biology and Oncology INMO, Wadmedani, Sudan, during the period 2000-2005 was conducted. Parameters included in the review were histological types of NPC according to the World Health Organization WHO classification, age, gender, locality, ethnicity, and stage. All cases of NPC with positive histology were included while other types of histology lymphoma, sarcoma were excluded. The SPSS software was used for data entry and analysis. RESULTS: Total number of patients with NPC was 103. Age range from 11-82 years, median was 41 years, and mean was 45.5 years of age. Male:female ratio was 2:1. The WHO histology type-3 was 73.8% of cases, WHO type-2 was 26.2%, and there was no case of WHO type-1 found in this study population. Neck swelling is the most common presenting symptom 77.8%. CONCLUSION: Pattern of NPC classification resembles those seen in endemic areas like South China. Dominant histology was WHO type-3. Identifying risk factors for NPC in Sudan is required.

Wilms tumour in Sudan.

BACKGROUND: Wilms tumour is one of the commonest childhood solid tumours which has an excellent outlook in the developed world with 5-year overall survival exceeding 90%. There is little information from Sudan regarding Wilms tumour. PROCEDURE: Records of patients with Wilms tumour diagnosed and treated at Institute of Nuclear Medicine, Molecular Biology and Oncology (INMO) in the University of Gezira from May 1999 to June 2007 were reviewed. RESULTS: Thirty-seven children presented at a mean age of 4.1 years (range 2 months-13 years). The male to female ratio was 0.9-1. Abdominal swelling or mass was the commonest symptom. There was 1 child with Stage I (2.7%), 7 with stage II (18.9%), 25 with Stage III (67.6%) and 4 with Stage IV (10.8%). Following diagnosis 27% of children did not receive further treatment (5.4% died prior to treatment, 5.4% were not able to finance treatment and for the rest 16.2% no cause was identified). More than half of the children did not have a nephrectomy and only 4 (11%) completed treatment. CONCLUSIONS: The poor outlook is related to several factors. Delayed presentation, poor awareness of treatment options, lack of finances, no provision of food, lodging and transport, absence of paediatric trained staff are the obstacles to better outcomes. Empowering parents with information, giving chemotherapy prior to nephrectomy, training staff and establishing links with a tertiary cancer centre in the developed world are some of the options to improve survival.