Search

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we present a literature review of gallbladder Burkitt's lymphoma (BL) cases that includes also an unpublished case in an HIV-infected child, observed by our center. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy, and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. The patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. A biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH), especially in children.

Introduction: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin-Frankfurt-Münster (BFM) protocols and compare our results with the original BFM reports., Methods: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997-2007 and 2008-2018 cohorts were analyzed separately., Results: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997-2007 period, respectively, 88% and 80% (BFM standard risk group-SRG), 75% and 67% (intermediate risk group-IRG), and 48% and 33% (high-risk group-HRG). The corresponding numbers for the 2008-2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM., Conclusion: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.

Lymphomas related to HIV are generally aggressive and have a poor prognosis, despite the use of combined antiretroviral therapy (cART) and effective chemotherapy treatment. To determine survival and prognostic factors in children and adolescents living with HIV (CLWH) in Rio de Janeiro (RJ), Brazil, who developed lymphomas, we performed a retrospective and observational study of vertically infected CLWH aged from 0 to 20 incomplete years during1995 to 2018 at five reference centers for cancer and HIV/AIDS treatment. Of the 25 lymphomas, 19 were AIDS-defining malignancies (ADM) and 6 were non-AIDS-defining malignancies (NADM). The 5-year overall survival (OS) and 5-year event-free survival (EFS) probabilities were both 32.00% (95% CI = 13.72-50.23%), and the 5-year disease-free survival (DFS) probability was 53.30% (95% CI = 28.02-78.58%). In the multivariate Cox regression analysis, performance status 4 (PS 4) was considered a poor prognostic factor for OS (HR 4.85, 95% CI = 1.81-12.97, p = 0.002) and EFS (HR 4.95, 95% CI = 1.84-13.34, p = 0.002). For the DFS, higher CD4+ T-cell counts were considered a better prognostic factor (HR 0.86, 95% CI = 0.76-0.97, p = 0.017) in the multivariate Cox regression analysis. This study demonstrates, for the first time, survival and prognostic factors for CLWH who developed lymphomas in RJ, Brazil.

The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0−20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09−2.50). ADM development IR decreased from 2.09−1.75−0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson−Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era., Competing Interests: The authors declare no conflict of interest.

Background: Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely., Methods: Using results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR)., Results: In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h 2  = 64%) and blood pressure (sBP h 2  = 29%, dBP, h 2  = 11%) were significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72 polymorphisms (P = 0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident., Conclusions: While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.

Objective: The aim of the study was to evaluate blood leukocyte counts in patients with uterine cervical neoplasia., Methods: Patients treated at a university hospital were reviewed retrospectively. Disease progression was monitored, beginning in 1990 to 2002, for at least 5 years. Blood count parameters included absolute leukocyte, neutrophil and lymphocyte counts, leukocytosis (white blood cells > 10³/μL), neutrophilia (neutrophils ≥ 70% of leukocytes), lymphopenia (lymphocytes ≤ 15% of leukocytes), and the neutrophil-lymphocyte ratio (NLR), categorized as less than 5 or 5 or greater., Results: A total of 315 patients were enrolled: 182 (57.8%) with preinvasive neoplasia (cervical intraepithelial neoplasia [CIN] group), 95 (30.1%) with stages I to II (early group), and 38 patients (12.1%) with stages III to IV neoplasia (advanced group). Neutrophil and lymphocyte counts were elevated and reduced, respectively, at advanced stages compared with the CIN group (P < 0.05). Leukocytosis, neutrophilia, lymphopenia, and an NLR of 5 or greater were more frequent at advanced stages compared with the CIN and early-stage groups (P < 0.05). Moreover, neutrophilia was also significantly more frequent at early stage compared with the CIN group. The advanced group with neutrophilia had increased frequency of recidivism and metastasis than patients in the CIN group with neutrophilia (P < 0.05)., Conclusions: Patients with advanced cervical cancer had significantly higher frequency of leukocyte alterations, although they may occur apart from the preinvasive stages. Overall, neutrophilia was the best indicator of cancer invasiveness.

Genetic variation of fatty acid binding protein 2 (FABP2) may contribute to the high prevalence of obesity and Type II diabetes in Tonga. To explore this we assessed the frequency of the FABP2 Ala54Thr polymorphism, obesity, and Type II diabetes in Tongans and possible inter-relationships. We investigated 1022 Tongan subjects, 433 men and 589 women aged 15-85 years, to identify possible associations between the FABP2 Ala54Thr polymorphism, obesity, Type II diabetes, BMI, glucose tolerance and standard lipid variables. The prevalence of the polymorphism was compared with that reported for other ethnic populations (studies from: Japanese, Finnish, African American, Native Canadian and Inuit, Swedish, Guadeloupe Indians, European males, and Caucasian populations). We found that 84% of the Tongan men and 93% of the Tongan women were overweight or obese (BMI> or =25kg/m2). The mean BMI+/-SD was not significantly different among those who were and were not carrying the Thr allele (males: Ala/Ala 30.4+/-5.4 and Thr carriers 29.8+/-5.1; females: Ala/Ala 33.8+/-6.4 and Thr carriers 33.6+/-5.1). The genotype frequencies were 76.2% Ala/Ala, 22.8% Ala/Thr, and 1.0% Thr/Thr. The Alal/Ala frequency is higher than the prevalences reported for all populations studied. The Thr allele was significantly associated with lower total cholesterol and LDL cholesterol in both sexes and in women also with lower HDL cholesterol. We conclude that there is a high prevalence of the FABP2 Ala54Thr polymorphism in Tongans. The polymorphism may be involved in lipid metabolism as the Thr allele is associated with low total and LDL cholesterol levels in this population.

We compared the current prevalence of increased BMI and type 2 diabetes in a representative group of Tongan subjects with measurements made in 1973, and we determined the distribution and possible interrelations with the UCP2 insertion/deletion (ins/del) polymorphism of these variables. We documented the BMI, glucose tolerance, and standard lipid variables in 1012 Tongan subjects (429 men and 583 women, ages 15 to 85 years) during 1998 and 2000 and compared the BMI findings with those of the 1973 survey. We also genotyped for the UCP2 ins/del polymorphism, assessed its association with obesity and type 2 diabetes, and compared its prevalence with those reported for other ethnic populations. The mean BMI +/- SD was greatly increased in both men (30.2 +/- 5.4 kg/m(2)) and women (33.8 +/- 6.2 kg/m(2)), representing increases since 1973 of 11.9% and 19.4%, respectively. The genotype frequencies were 97% for the del/del genotype and 3% for the ins/del genotype; we found no ins/ins homozygotes. This distribution is strikingly different from those reported for white, South Indian, Pima Native-American, and Asian populations (49 to 77% for del/del genotype). We conclude that there is a marked prevalence of obesity in Tonga, a prevalence that has increased since 1973. We also conclude that there is a unique, near-uniform distribution of the UCP2 45-bp ins/del polymorphism in Tongans. This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga.

As there is a high prevalence of obesity in Tonga, we aimed to determine the distribution of the beta2 adrenoceptor gene Gln(27)Glu polymorphism and to assess its relevance to obesity and to Type II diabetes, known to be prevalent in that population. A random sample of 1022 individuals from Tonga were genotyped for the Gln(27)Glu polymorphism in the beta 2 adrenoceptor gene. To assess the prevalence of obesity we measured body-mass index (BMI), fat-free mass, percentage fat and waist-to-hip ratio (WHR). To assess glucose metabolism we measured HbA(1c), fasting blood glucose, fasting serum insulin, and 1- and 2-h glucose; we also measured serum lipid and creatinine levels. We found that 84% of the Tongan men and 93% of the women were overweight or obese (BMI > or = 25 kg/m(2)) and 15.1% had Type II diabetes. Genotype frequencies among the 1022 Tongans were: Gln/Gln 90.3% and Gln/Glu 9.6%; we found one Glu/Glu homozygote. The mean BMI (+/-S.D.) for men was not significantly different for those who were homozygous (30.2+/-5.4 kg/m(2)) or heterozygous (30.1+/-5.5 kg/m(2)) for the Gln allele; this was also true for women (33.7+/-6.2 kg/m(2) for homozygous and 34.0+/-5.6 kg/m(2) for heterozygous). The Glu allele was not associated with other measures of obesity or abnormal glucose metabolism in this generally overweight population. There is a unique frequency of the Gln/Glu beta 2 adrenoceptor polymorphism among Tongans. We found no association of the polymorphism with obesity measures or Type II diabetes-related variables in the Tongan population among whom we documented a high prevalence of obesity and Type II diabetes and a low frequency of the Glu allele.

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population.