The Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis examined long-term glomerular dysfunction in childhood cancer survivors

This investigation aimed to evaluate glomerular dysfunction among childhood cancer survivors in comparison with matched controls from the general population. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis, a nationwide cross-sectional cohort study, 1024 survivors five or more years after diagnosis, aged 18 or more years at study, treated between 1963-2001 with nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide or hematopoietic stem cell transplantation participated. In addition, 500 age- and sex-matched controls from Lifelines, a prospective population-based cohort study in the Netherlands, participated. At a median age of 32.0 years (interquartile range 26.6-37.4), the glomerular filtration rate was under 60 ml/min/1.73m2 in 3.7% of survivors and in none of the controls. Ten survivors had kidney failure. Chronic kidney disease according to age-thresholds (glomerular filtration rate respectively under 75 for age under 40, under 60 for ages 40-65, and under 40 for age over 65) was 6.6% in survivors vs. 0.2% in controls. Albuminuria (albumin-to-creatinine ratio over3 mg/mmol) was found in 16.2% of survivors and 1.2% of controls. Risk factors for chronic kidney disease, based on multivariable analyses, were nephrectomy (odds ratio 3.7 (95% Confidence interval 2.1-6.4)), abdominal radiotherapy (1.8 (1.1-2.9)), ifosfamide (2.9 (1.9-4.4)) and cisplatin over 500 mg/m2 (7.2 (3.4-15.2)). For albuminuria, risk factors were total body irradiation (2.3 (1.2-4.4)), abdominal radiotherapy over 30 Gy (2.6 (1.4- 5.0)) and ifosfamide (1.6 (1.0-2.4)). Hypertension and follow-up 30 or more years increased the risk for glomerular dysfunction. Thus, lifetime monitoring of glomerular function in survivors exposed to these identified high risk factors is warranted.</p

Hypertension in long-term childhood cancer survivors after treatment with potentially nephrotoxic therapy; DCCSS-LATER 2:Renal study

Purpose: To evaluate the prevalence of and risk factors for hypertension in childhood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (≥1 g/m2 per single dose or ≥10 g/m2 total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic ≥140 and/or diastolic ≥90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic ≥135 and/or diastolic ≥85, night time: systolic ≥120 and/or diastolic ≥70, 24-h: systolic ≥130 and/or diastolic ≥80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Results: Median age at cancer diagnosis was 4.7 years (interquartile range, IQR 2.4–9.2), at study 32.5 years (IQR 27.7–38.0) and follow-up 25.5 years (IQR 21.4–30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (<60 ml/min/1.73 m2) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4–8.5). Risk factors were abdominal radiotherapy ≥20 Gy and TBI. The ABPM-pilot study (n = 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. Conclusion: The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy ≥20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND

The Value of IgM Memory B-Cells in the Assessment of Splenic Function in Childhood Cancer Survivors at Risk for Splenic Dysfunction:A DCCSS-LATER Study

Background: Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective: We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods: All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell-Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells &lt; 9 cells/µL was defined as abnormal. Results: We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/µL, p=0.06) or TBI (55 cells/µL, p = 0.03) compared to CCS who received splenectomy (20 cells/µL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/µL vs. 44 cells/µL). Conclusion: Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction.</p

Different ventilation strategies affect lung function but do not increase tumor necrosis factor-α and prostacyclin production in lavaged rat lungs in vivo

Background: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. Methods: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, veneration with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-α (TNF-α) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. Results: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-α levels between groups. Serum PGI2 and TNF-α levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. Conclusions: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI2 and TNF-α release, nor of pulmonary TNF-α release. Mechanical ventilation at high mean airway pressure levels increased PGI2 levels in the bronchoalveolar lavage- accessible space

Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study

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Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age

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The Value of IgM Memory B-Cells in the Assessment of Splenic Function in Childhood Cancer Survivors at Risk for Splenic Dysfunction:A DCCSS-LATER Study

Background. Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective. We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods. All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell-Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells &lt; 9 cells/μL was defined as abnormal. Results. We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/μL, p=0.06) or TBI (55 cells/μL, p = 0.03) compared to CCS who received splenectomy (20 cells/μL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/μL vs. 44 cells/μL). Conclusion. Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction.</p

The Value of IgM Memory B-Cells in the Assessment of Splenic Function in Childhood Cancer Survivors at Risk for Splenic Dysfunction:A DCCSS-LATER Study

Background. Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective. We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods. All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell-Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells &lt; 9 cells/μL was defined as abnormal. Results. We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/μL, p=0.06) or TBI (55 cells/μL, p = 0.03) compared to CCS who received splenectomy (20 cells/μL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/μL vs. 44 cells/μL). Conclusion. Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction.</p

Late Mortality in Childhood Cancer Survivors according to Pediatric Cancer Diagnosis and Treatment Era in the Dutch LATER Cohort

This multi-center cohort-study examined late mortality among 6,165 Dutch five-year childhood cancer survivors diagnosed 1963-2001. Clinical details and cause of death were based on medical records. Mortality was 12-fold that of the general population, with 51.3 additional deaths per 10,000 person-years (21.9 yrs median follow-up). Cumulative mortality 15 yrs post-diagnosis was 6.9%, predominantly from late recurrences; thereafter the absolute contribution of other health outcomes increased. Cumulative all-cause and recurrence-related mortality were highest for Central Nervous System and bone tumor survivors. All-cause, but not subsequent tumor and circulatory disease-related cumulative mortality, was highest for patients diagnosed 1963-1979 vs. later (p-trend <0.001)