Gideon K. D. Zamba

The Risk of Developing Arm Lymphedema Among Breast Cancer Survivors: A Meta-Analysis of Treatment Factors

BackgroundAs more women survive breast cancer, long-term complications that affect quality of life, such as lymphedema of the arm, gain greater importance. Numerous studies have attempted to identify treatment and prognostic factors for arm lymphedema, yet the magnitude of these associations remains inconsistent.MethodsA PubMed search was conducted through January 2008 to locate articles on lymphedema and treatment factors after breast cancer diagnosis. Random-effect models were used to estimate the pooled risk ratio.ResultsThe authors identified 98 independent studies that reported at least one risk factor of interest. The risk ratio (RR) of arm lymphedema was increased after mastectomy when compared with lumpectomy [RR = 1.42; 95% confidence interval (CI) 1.15–1.76], axillary dissection compared with no axillary dissection (RR = 3.47; 95% CI 2.34–5.15), axillary dissection compared with sentinel node biopsy (RR = 3.07; 95% CI 2.20–4.29), radiation therapy (RR = 1.92; 95% CI 1.61–2.28), and positive axillary nodes (RR = 1.54; 95% CI 1.32–1.80). These associations held when studies using self-reported lymphedema were excluded.ConclusionsMastectomy, extent of axillary dissection, radiation therapy, and presence of positive nodes increased risk of developing arm lymphedema after breast cancer. These factors likely reflected lymph node removal, which most surgeons consider to be the largest risk factor for lymphedema. Future studies should consider examining sentinel node biopsy versus no dissection with a long follow-up time post surgery to see if there is a benefit of decreased lymphedema compared with no dissection.

Prevalence of Duchenne and Becker Muscular Dystrophies in the United States

OBJECTIVE: To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]). METHODS: In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10 000 boys, ages 5 to 9 years, for 4 quinquennia (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and prevalence per 10 000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype. RESULTS: Overall, 649 cases resided in an MD STARnet site during ≥1 quinquennia. Prevalence estimates per 10 000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991–1995, 1996–2000, 2001–2005, and 2006–2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10 000 male individuals, ages 5 to 24 years. CONCLUSIONS: We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.

Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction

Background Diagnosis of chronic obstructive pulmonary disease is based on detection of airflow obstruction on spirometry. There is no consensus regarding using a fixed threshold to define airflow obstruction versus using the lower limit of normal (LLN) adjusted for age. We compared the accuracy and discrimination of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended fixed ratio of forced expiratory volume in the first second/forced vital capacity<0.70 with LLN in diagnosing smoking-related airflow obstruction using CT-defined emphysema and gas trapping as the disease gold standard. Methods Data from a large multicentre study (COPDGene), which included current and former smokers (age range 45–80 years) with and without airflow obstruction, were analysed. Concordance between spirometric thresholds was measured. The accuracy of the thresholds in diagnosing emphysema and gas trapping was assessed using quantitative CT as gold standard. Results 7743 subjects were included. There was very good agreement between the two spirometric cutoffs (κ=0.85; 95% CI 0.83 to 0.86, p<0.001). 7.3% were discordant. Subjects with airflow obstruction by fixed ratio only had a greater degree of emphysema (4.1% versus 1.2%, p<0.001) and gas trapping (19.8% vs 7.5%, p<0.001) than those positive by LLN only, and also smoking controls without airflow obstruction (4.1% vs 1.9% and 19.8% vs 10.9%, respectively, p<0.001). On follow-up, the fixed ratio only group had more exacerbations than smoking controls. Conclusions Compared with the fixed ratio, the use of LLN fails to identify a number of patients with significant pulmonary pathology and respiratory morbidity.

Incidence, Survival and Prevalence of Neuroendocrine Tumors versus Neuroblastoma in Children and Young Adults: Nine Standard SEER Registries, 1975–2006

The incidence, survival, and prevalence of neuroendocrine tumors (NETs) in children were determined as a first step in improving diagnosis and therapy. Outcomes were compared with neuroblastoma, a pediatric malignancy that shares several biomarkers.

Morphological parameters for assessment of burn severity in an acute burn injury rat model

Determination of burn severity (i.e. burn depth) is important for effective medical management and treatment. Using a recently described acute burn model, we studied various morphological parameters to detect burn severity. Anaesthetized Sprague–Dawley rats received burns of various severity (0‐ to14‐s contact time) followed by standard resuscitation using intravenous fluids. Biopsies were taken from each site after 5 h, tissues fixed in 10% neutral‐buffered formalin, processed and stained with haematoxylin and eosin. Superficial burn changes in the epidermis included early keratinocyte swelling progressing to epidermal thinning and nuclear elongation in deeper burns. Subepidermal vesicle formation generally decreased with deeper burns and typically contained grey foamy fluid. Dermal burns were typified by hyalinized collagen and a lack of detectable individual collagen fibres on a background of grey to pale eosinophilic seroproteinaceous fluid. Intact vascular structures were identified principally deep to the burn area in the collagen. Follicle cell injury was identified by cytoplasmic clearing/swelling and nuclear pyknosis, and these follicular changes were often the deepest evidence of burn injury seen for each time point. Histological scores (epidermal changes) or dermal parameter depths (dermal changes) were regressed on burn contact time. Collagen alteration (r2 = 0.91) correlated best to burn severity followed by vascular patency (r2 = 0.82), epidermal changes (r2 = 0.76), subepidermal vesicle formation (r2 = 0.74) and follicular cell injury was useful in all but deep burns. This study confirms key morphological parameters can be an important tool for the detection of burn severity in this acute burn model.

Validation of a Novel Physical Activity Assessment Device in Morbidly Obese Females

Assessment of physical activity in morbidly obese subjects is important especially in bariatric surgery. We examined the validity of Intelligent Device for Energy Expenditure and Activity (IDEEA) for measuring physical activity and sedentary behavior in morbidly obese women. Activity types, gait counts, and speed detected by the IDEEA monitor were compared to those reported by an observer. The IDEEA monitor detected activity types and gait counts with relatively high accuracy, although slightly lower in extremely obese women than in normal weight controls. The IDEEA monitor accurately estimated gait speeds in both groups. Since gait speed predicts energy expenditure more accurately than gait counts, it is of greater clinical relevance. Reliability of the IDEEA monitor was excellent. The IDEEA monitor is a valid instrument for measuring physical activity and sedentary behavior in extremely obese women, and therefore has potential applications in bariatric surgery both in preoperative evaluation and long-term follow-up.

Repeatability of gallium-68 DOTATOC positron emission tomographic imaging in neuroendocrine tumors.

Objective To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors. Methods Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured. The repeatability of these measurements was investigated. Results Forty-seven target lesions were identified on whole-body PET and 21 lesions on dynamic images. There was excellent repeatability with intraclass correlation coefficient of 0.99 for SUVmax, SUVmean, and K-Patlak, and 0.85 for K-influx. The median absolute percent differences and the interquartile ranges (IQR) between 2 scans for SUVmax and SUVmean were 7.4% (IQR, 14.1%) and 9.3% (IQR, 10.6%), respectively. The median absolute percent differences for K-Patlak and K-influx were 12.5% (IQR, 12.6%) and 29.9% (IQR, 22.4%), respectively. The SUVmax of target lesions did not differ by more than 25% between the 2 scans. Conclusions 68Ga-DOTATOC PET imaging of neuroendocrine tumors is highly reproducible. A difference of more than 25% in SUVmax represents a change that is larger than the measurement error observed on repeated studies and should reflect a significant change in the biological character of the tumor.

State-space models for count time series with excess zeros

Count time series are frequently encountered in biomedical, epidemiological and public health applications. In principle, such series may exhibit three distinctive features: overdispersion, zero-inflation and temporal correlation. Developing a modelling framework that is sufficiently general to accommodate all three of these characteristics poses a challenge. To address this challenge, we propose a flexible class of dynamic models in the state-space framework. Certain models that have been previously introduced in the literature may be viewed as special cases of this model class. For parameter estimation, we devise a Monte Carlo Expectation-Maximization (MCEM) algorithm, where particle filtering and particle smoothing methods are employed to approximate the high-dimensional integrals in the E-step of the algorithm. To illustrate the proposed methodology, we consider an application based on the evaluation of a participatory ergonomics intervention, which is designed to reduce the incidence of workplace injuries among a group of hospital cleaners. The data consists of aggregated monthly counts of work-related injuries that were reported before and after the intervention.

90Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy

Pretherapy PET with 86Y-DOTATOC is considered the ideal dosimetry protocol for 90Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for 90Y-DOTATOC using 90Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of 90Y-DOTATOC therapy in patients with somatostatin receptor–positive tumors. 90Y-DOTATOC was given in 3 cycles 6–8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m2; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight 90Y-DOTATOC PET/CT at 5 h after therapy and 90Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of 90Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of 90Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of 90Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of 90Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of 90Y-DOTATOC is feasible using 90Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.

Screening Patients with Esophageal Cancer to Determine Eligibility for Adjuvant Treatment Trials

Background: The tolerability of adjuvant chemotherapy in esophageal cancer is unclear. Patients and Methods: This was a phase II trial of adjuvant paclitaxel in patients with esophageal cancer after trimodality treatment. Patients with residual viable tumor after resection were eligible for study inclusion. Treatment was 80 mg/m2 paclitaxel intravenously on days 1, 8, and 15 every 28 days for total of two cycles. The primary objective was to determine whether 75% or more of the patients would tolerate 240 mg/m2 or more of paclitaxel, which corresponded to 50% or more of the total planned dose. Results: Eleven out of the 12 enrolled patients (92%, 95% confidence interval (CI)=62-100%) were able to complete at least 50% of the planned paclitaxel dose. Median progression-free survival was 7 months (95% CI=2-28 months). Median overall survival was 28 months (95% CI=12-36 months). Only one patient experienced a grade 4 adverse event. Conclusion: Screening patients with esophageal cancer after trimodality treatment might improve completion of adjuvant trials.