Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. CONCLUSIONS AND RELEVANCE: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00849615.info:eu-repo/semantics/publishedVersio

Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression:A marker of malignant potential?

Peer reviewedPublisher PD

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes

Background The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). Methods The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. Results Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. Conclusions A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

Presence of S100A9-positive inflammatory cells in cancer tissues correlates with an early stage cancer and a better prognosis in patients with gastric cancer

BACKGROUND: S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression. METHODS: S100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated. RESULTS: S100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells. CONCLUSIONS: Our results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis

Empirical Modeling of Planetary Boundary Layer Dynamics Under Multiple Precipitation Scenarios Using a Two-Layer Soil Moisture Approach: An Example From a Semiarid Shrubland

In semiarid regions, where water resources are limited and precipitation dynamics are changing, understanding land surface-atmosphere interactions that regulate the coupled soil moisture-precipitation system is key for resource management and planning. We present a modeling approach to study soil moisture and albedo controls on planetary boundary layer height (PBLh). We used Santa Rita Creosote Ameriflux and Tucson Airport atmospheric sounding data to generate empirical relationships between soil moisture, albedo, and PBLh. Empirical relationships showed that similar to 50% of the variation in PBLh can be explained by soil moisture and albedo with additional knowledge gained by dividing the soil profile into two layers. Therefore, we coupled these empirical relationships with soil moisture estimated using a two-layer bucket approach to model PBLh under six precipitation scenarios. Overall we observed that decreases in precipitation tend to limit the recovery of the PBL at the end of the wet season. However, increases in winter precipitation despite decreases in summer precipitation may provide opportunities for positive feedbacks that may further generate more winter precipitation. Our results highlight that the response of soil moisture, albedo, and the PBLh will depend not only on changes in annual precipitation, but also on the frequency and intensity of this change. We argue that because albedo and soil moisture data are readily available at multiple temporal and spatial scales, developing empirical relationships that can be used in land surface-atmosphere applications have great potential for exploring the consequences of climate change.University of Arizona College of Agriculture and Life Sciences (CALS); Arizona University System Technology and Research Initiative Fund (TRIF); University of Arizona Office of the Vice President for Research (VPR); SAHRA (Sustainability of Semi-Arid Hydrology and Riparian area) under the STC Program of the National Science Foundation (NSF), NSF CAREER [EAR-1255013]; UA Springfield Scholarship for Graduate Research in Rangelands; UA William A. Calder III PhD Scholarship for Mexican graduate students focused in conservation; UA Kel M. Fox Watershed Scholarship6 month embargo; published online: 10 November 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]