[Migraine and mitochondrial diseases : Energy deficit in the brain]. / Migräne und mitochondriale Erkrankungen : Energiedefizit im Gehirn.

Mitochondrial diseases are complex metabolic disorders caused by genetic mutations and lead to impaired energy production in the mitochondria of cells. The clinical spectrum ranges from severe multiorgan involvement in early childhood to mild monosymptomatic courses in adulthood. The brain, heart, and skeletal muscles are particularly affected due to their high energy demands. Headaches in general and migraine in particular, occur disproportionately more frequently in patients with mitochondrial diseases. In recent years similarities in the pathomechanism of mitochondrial diseases and migraine have been investigated in numerous biochemical, genetic, and therapeutic studies. The results suggest a dysfunctional energy metabolism with demonstrable mitochondrial damage as a central aspect in the pathogenesis of migraine. These findings are valuable for a better understanding of primary headache disorders and mitochondrial diseases as well as for the optimization of diagnostic and treatment procedures and should be applied in the clinical practice.

Guideline Concordance of Treatment and Outcomes Among Adult Non-Hodgkin Lymphoma Patients in Sub-Saharan Africa: A Multinational, Population-Based Cohort.

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

BACKGROUND: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. METHODS: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). RESULTS: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. CONCLUSIONS: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

[Migraine and mitochondrial diseases : Energy deficit in the brain]. / Migräne und mitochondriale Erkrankungen : Energiedefizit im Gehirn.

Mitochondrial diseases are complex metabolic disorders caused by genetic mutations and lead to impaired energy production in the mitochondria of cells. The clinical spectrum ranges from severe multiorgan involvement in early childhood to mild monosymptomatic courses in adulthood. The brain, heart, and skeletal muscles are particularly affected due to their high energy demands. Headaches in general and migraine in particular, occur disproportionately more frequently in patients with mitochondrial diseases. In recent years similarities in the pathomechanism of mitochondrial diseases and migraine have been investigated in numerous biochemical, genetic, and therapeutic studies. The results suggest a dysfunctional energy metabolism with demonstrable mitochondrial damage as a central aspect in the pathogenesis of migraine. These findings are valuable for a better understanding of primary headache disorders and mitochondrial diseases as well as for the optimization of diagnostic and treatment procedures and should be applied in the clinical practice.

Presentation, patterns of care, and outcomes of patients with prostate cancer in sub-Saharan Africa: A population-based registry study.

BACKGROUND: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA. METHODS: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs). RESULTS: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy. CONCLUSIONS: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.

Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence.

BACKGROUND: Cervical cancer (CC) is the most common female cancer in many countries of sub-Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS). METHODS: Our observational study covered nine population-based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44-125 patients diagnosed from 2010 to 2016 were selected in each. Cancer-directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines. RESULTS: Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline-adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow-up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline-adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I-III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36-8.37; HRR, 1.97; CI, 0.59-6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19-12.71) and no CDT (HRR, 9.43; CI, 3.03-29.33) showed substantially worse survival. CONCLUSION: We found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one-fifth and possibly up to two-thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients. IMPLICATIONS FOR PRACTICE: Despite evidence-based interventions including guideline-adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population-based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub-Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub-Saharan Africa to access timely and high-quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer-directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource-constrained circumstances.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.

BACKGROUND: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. METHODS: Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients ("traced patients"). Excess hazards of death by therapy use were modeled in a relative survival context. RESULTS: A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. CONCLUSIONS: Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.

Cancer in Africa 2018: The role of infections.

We estimate the fractions of cancer attributed to infections in Africa in 2018. The number of new cancer cases occurring was taken from Globocan2018 with some additional estimations based on data from African population-based registries. Population attributable fractions were calculated using prevalence of infection and relative risk in exposed vs. nonexposed. The greatest share of infection-associated cancers is due to the human papillomaviruses (12.1% of all cancers in Africa and 15.4% in sub-Saharan Africa [SSA]); of these, cervical cancer is by far the most common. Kaposi sarcoma-associated herpesvirus is responsible for 3.1% of all cancers in Africa, the hepatitis viruses (B and C) for 2.9% and Helicobacter pylori for 2.7% (non-Cardia Gastric cancer and primary gastric lymphomas). Two percent of cancers are attributable to the Epstein-Barr virus, Schistosoma haematobium increases the risk of bladder cancer resulting in 1.0% of all cancers. HIV-related NHL and squamous cell carcinoma of the conjunctiva account for 0.6% of cancers. Altogether 24.5% of cancers in Africa and 28.7% in SSA are due to infectious agents. Infections are by far the most common cancer risk factor for cancer in Africa-the traditional risk factors (smoking, alcohol and unhealthy diet) probably cause only one in eight cancers in Africa. Prevention should focus on those infectious diseases preventable through vaccination (HPV and hepatitis B) which could reduce two-thirds of the burden. Helicobacter pylori and schistosomiasis are treatable with antibiotics and praziquantel, with a potential reduction of one in eight infection-associated cancers.

Clinical presentation and diagnosis of adult patients with non-Hodgkin lymphoma in Sub-Saharan Africa.

Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in Sub-Saharan Africa (SSA). Comprehensive diagnostics of NHL are essential for effective treatment. Our objective was to assess the frequency of NHL subtypes, disease stage and further diagnostic aspects. Eleven population-based cancer registries in 10 countries participated in our observational study. A random sample of 516 patients was included. Histological confirmation of NHL was available for 76.2% and cytological confirmation for another 17.3%. NHL subclassification was determined in 42.1%. Of these, diffuse large B cell lymphoma, chronic lymphocytic leukaemia and Burkitt lymphoma were the most common subtypes identified (48.8%, 18.4% and 6.0%, respectively). We traced 293 patients, for whom recorded data were amended using clinical records. For these, information on stage, human immunodeficiency virus (HIV) status and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was available for 60.8%, 52.6% and 45.1%, respectively. Stage at diagnosis was advanced for 130 of 178 (73.0%) patients, HIV status was positive for 97 of 154 (63.0%) and ECOG PS was ≥2 for 81 of 132 (61.4%). Knowledge about NHL subclassification and baseline clinical characteristics is crucial for guideline-recommended treatment. Hence, regionally adapted investments in pathological capacity, as well as standardised clinical diagnostics, will significantly improve the therapeutic precision for NHL in SSA.

The burden of Burkitt lymphoma in Africa.

BACKGROUND: Burkitt lymphoma (BL) is a relatively common cancer of childhood in tropical Africa, although its precise incidence and continent-wide geographic distribution have not been previously systematically studied. METHODS: Using the methods employed to produce national estimates of cancer incidence for the "Globocan" series of the International Agency for Research on Cancer, along with detailed information on cancer incidence by histological subtype from cancer registries in Africa, we estimate the numbers and rates of incidence by sex, age group, country and region of Africa. RESULTS: We estimate that the number of new cases that occurred in 2018 to be about 3900, two thirds in males, and 81% in children aged 0-14. On a national basis, the geographic distribution of incidence rates among children in sub-Saharan Africa resembles that of the prevalence of infection with Falciparum malaria. An estimated 81% of cases are associated with infection with Epstein Barr virus (EBV). CONCLUSIONS: BL comprises almost 50% of childhood of non-Hodgkin lymphoma in Africa, almost all of which are associated with EBV, with the geographic distribution - at least in sub Saharan Africa - mediated by infection with malaria.

The burden of squamous cell carcinoma of the conjunctiva in Africa.

Squamous cell carcinoma of the conjunctiva (SCCC) is a relatively common cancer in Africa, although its precise incidence and geographic distribution have not been previously systematically studied. METHODS: Using the methods employed to produce national estimates of cancer incidence for the "Globocan" series of the International Agency for Research on Cancer, along with detailed information on cancer incidence by histological subtype from cancer registries in Africa, we estimate the numbers and rates of incidence by sex, age group, country and region of Africa. RESULTS: We estimate that the number of new cases occurring in 2018 to be about 6 200, with all but about 50 in sub Saharan Africa, and 55% in females. On a national basis, the geographic distribution of incidence rates resembles that of the prevalence of infection with HIV, with a strong correlation between them, especially in males. CONCLUSIONS: We estimate that about one third of the total cases of SCCC occurring in Africa are HIV-related.