Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy. METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed. RESULTS: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival. CONCLUSIONS: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.

Subacute neural stem cell therapy for traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) frequently results in devastating and prolonged morbidity. Cellular therapy is a burgeoning field of experimental treatment that has shown promise in the management of many diseases, including TBI. Previous work suggests that certain stem and progenitor cell populations migrate to sites of inflammation and improve functional outcome in rodents after neural injury. Unfortunately, recent study has revealed potential limitations of acute and intravenous stem cell therapy. We studied subacute, direct intracerebral neural stem and progenitor cell (NSC) therapy for TBI. MATERIALS AND METHODS: The NSCs were characterized by flow cytometry and placed (400,000 cells in 50 muL 1x phosphate-buffered saline) into and around the direct injury area, using stereotactic guidance, of female Sprague Dawley rats 1 wk after undergoing a controlled cortical impact injury. Immunohistochemistry was used to identify cells located in the brain at 48 h and 2 wk after administration. Motor function was assessed using the neurological severity score, foot fault, rotarod, and beam balance. Cognitive function was assessed using the Morris water maze learning paradigm. Repeated measures analysis of variance with post-hoc analysis were used to determine significance at P < 0.05. RESULTS: Immunohistochemistry analysis revealed that 1.4-1.9% of infused cells remained in the neural tissue at 48 h and 2 wk post placement. Nearly all cells were located along injection tracks at 48 h. At 2 wk some cell dispersion was apparent. Rotarod motor testing revealed significant increases in maximal speed among NSC-treated rats compared with saline controls at d 4 (36.4 versus 27.1 rpm, P < 0.05) and 5 (35.8 versus 28.9 rpm, P < 0.05). All other motor and cognitive evaluations were not significantly different compared to controls. CONCLUSIONS: Placement of NSCs led to the cells incorporating and remaining in the tissues 2 wk after placement. Motor function tests revealed improvements in the ability to run on a rotating rod; however, other motor and cognitive functions were not significantly improved by NSC therapy. Further examination of a dose response and optimization of placement strategy may improve long-term cell survival and maximize functional recovery.

A formative evaluation of the American Diabetes Association's Choosing Health and Sensible Exercise childhood obesity intervention

Background. The increasing prevalence of overweight among youth in the United States, and the parallel rise in related medical comorbidities has led to a growing need for efficient weight-management interventions. Purpose. The aim of this study was to evaluate the effects of the Choosing Health and Sensible Exercise (C.H.A.S.E.) childhood obesity prevention program on Body Mass Index (BMI), physical activity and dietary behaviors. Methods. This study utilized de-identified data collected during the fall 2006 session of the C.H.A.S.E. program. A total of 65 students at Woodview Elementary School and Deepwater Elementary School participated in this intervention. The C.H.A.S.E. program is a 10-week obesity prevention program that focuses on nutrition and physical activity education. Collection of height and weight data, and a health behavior survey was conducted during the first and last week of the intervention. Paired t-tests were used to determine statistically significant differences between pre- and post-intervention measurements. One-way analysis of variance was used to adjust for potential confounders, such as gender, age, BMI category ("normal weight", "at risk overweight", or "overweight"), and self-reported weight loss goals. Data were analyzed using STATA, v. 9.2. Results. A significant decrease in mean BMI (p< 0.05) was found after the 10-week intervention. While the results were statistically significant for the group as a whole, changes in BMI were not significant when stratified by age, sex, or ethnicity. The mean overall scores for the behavior survey did not change significantly pre- and post-intervention; however, significant differences were found in the dietary intention scale, indicating that students were more likely to intend to make healthier food choices (p<0.05). No statistically significant decreases in BMI were found when stratified for baseline BMI-for-age percentiles or baseline weight loss efforts (p>0.05). Conclusion. The results of this evaluation provide information that will be useful in planning and implementing an effective childhood obesity intervention in the future. Changes in the self-reported dietary intentions and BMI show that the C.H.A.S.E. program is capable of modifying food choice selection and decreasing BMI. Results from the behavior questionnaire indicate that students in the intervention program were making changes in a positive direction. Future implementation of the C.H.A.S.E. program, as well as other childhood obesity interventions, may want to consider incorporating additional strategies to increase knowledge and other behavioral constructs associated with decreased BMI. In addition, obesity prevention programs may want to increase parental involvement and increase the dose or intensity of the intervention. ^

Performance recovery from exercise: A review from a statistical point of view

Background. Research into methods for recovery from fatigue due to exercise is a popular topic among sport medicine, kinesiology and physical therapy. However, both the quantity and quality of studies and a clear solution of recovery are lacking. An analysis of the statistical methods in the existing literature of performance recovery can enhance the quality of research and provide some guidance for future studies. Methods: A literature review was performed using SCOPUS, SPORTDiscus, MEDLINE, CINAHL, Cochrane Library and Science Citation Index Expanded databases to extract the studies related to performance recovery from exercise of human beings. Original studies and their statistical analysis for recovery methods including Active Recovery, Cryotherapy/Contrast Therapy, Massage Therapy, Diet/Ergogenics, and Rehydration were examined. Results: The review produces a Research Design and Statistical Method Analysis Summary. Conclusion: Research design and statistical methods can be improved by using the guideline from the Research Design and Statistical Method Analysis Summary. This summary table lists the potential issues and suggested solutions, such as, sample size calculation, sports specific and research design issues consideration, population and measure markers selection, statistical methods for different analytical requirements, equality of variance and normality of data, post hoc analyses and effect size calculation.^

DEVELOPMENT OF A BEAM-SPECIFIC PLANNING TARGET VOLUME AND A ROBUST PLAN ANALYSIS TOOL FOR PROTON THERAPY

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of this dissertation research was to develop a treatment planning method and a planevaluation method that address proton-specific issues regarding setup and range uncertainties. Treatment plan designing method adapted to proton therapy: Currently, for proton therapy using a scanning beam delivery system, setup uncertainties are largely accounted for by geometrically expanding a clinical target volume (CTV) to a planning target volume (PTV). However, a PTV alone cannot adequately account for range uncertainties coupled to misaligned patient anatomy in the beam path since it does not account for the change in tissue density. In order to remedy this problem, we proposed a beam-specific PTV (bsPTV) that accounts for the change in tissue density along the beam path due to the uncertainties. Our proposed method was successfully implemented, and its superiority over the conventional PTV was shown through a controlled experiment.. Furthermore, we have shown that the bsPTV concept can be incorporated into beam angle optimization for better target coverage and normal tissue sparing for a selected lung cancer patient. Treatment plan evaluation method adapted to proton therapy: The dose-volume histogram of the clinical target volume (CTV) or any other volumes of interest at the time of planning does not represent the most probable dosimetric outcome of a given plan as it does not include the uncertainties mentioned earlier. Currently, the PTV is used as a surrogate of the CTV’s worst case scenario for target dose estimation. However, because proton dose distributions are subject to change under these uncertainties, the validity of the PTV analysis method is questionable. In order to remedy this problem, we proposed the use of statistical parameters to quantify uncertainties on both the dose-volume histogram and dose distribution directly. The robust plan analysis tool was successfully implemented to compute both the expectation value and its standard deviation of dosimetric parameters of a treatment plan under the uncertainties. For 15 lung cancer patients, the proposed method was used to quantify the dosimetric difference between the nominal situation and its expected value under the uncertainties.