Association of BMI with overall survival in patients with mCRC who received chemotherapy versus EGFR and VEGF-targeted therapies

Although a raised body mass index (BMI) is associated with increased risk of colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the metastatic setting is limited. We compared overall survival (OS) across BMI groups for metastatic CRC, and specifically examined the effect of BMI within the group of patients treated with targeted therapies (TT). Retrospective data were obtained from the South Australian Registry for mCRC from February 2006 to October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m(2) , Normal = 18.5 to <25 kg/m(2) , Overweight = 25 to <30 kg/m(2) , Obese I = 30 to <35 kg/m(2) , Obese II ≥35 kg/m(2) . Of 1174 patients, 42 were underweight, 462 overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1 months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS was longer for normal versus overweight or obese I patients receiving chemotherapy + targeted therapy (35.7 vs 25.1 or 22.8 months, HR 1.59 and 1.63, respectively) with no difference in OS for chemotherapy alone. On breakdown by type of targeted therapy, overweight and obese I patients had a poorer outcome with Bevacizumab. The BMI is predictive of a poorer outcome for underweight and overweight patients in the whole population. Of those receiving chemotherapy and targeted therapy, BMI is an independent predictor for OS for overweight and obese I patients, specifically for those treated with Bevacizumab. Patients who are overweight or obese (group I) may be a target group for lifestyle and nutrition advice to improve OS with TT.Gargi S. Patel, Shahid Ullah, Carol Beeke, Paul Hakendorf, Robert Padbury, Timothy J. Price and Christos S. Karapeti

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines

Diagnostic and therapeutic strategies for acute biliary inflammation/ infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/ infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient's general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient's general medical condition. © Springer-Verlag Tokyo 2007.published_or_final_versio

Nitrogen Use in Durum and Selected Brassicaceae Oilseeds in Two-Year Rotations

Brassicaceae oilseeds can serve as potential feedstocks for renewable biofuels to offset demand for petroleum-based alternatives. However, little is known about oilseed crop yield potential and N use in semiarid, wheat (Triticum spp.)-based cropping systems that dominate the northern Great Plains (NGP). A 5-yr study was conducted in northeast Montana to investigate the yield potential of a direct seeded system of durum (T. durumDesf.) in rotation with either chemical fallow or three Brassicaceae oilseeds: camelina [Camelina sativa (L.) Crantz], crambe (Crambe abyssinica Hochst. ex R.E. Fries), and canola-quality Brassica juncea L. Overall, results from the study indicated that seed yield in the three Brassicaceae oilseeds tested in rotation with durum was related (P \u3c 0.001; r2 = 0.68) to a nitrogen recovery index (NRI), indicating the importance of nitrogen use (NU) efficiency in dryland oilseed production, and that B. juncea generally used N more efficiently than crambe and camelina. Similarly, NRI was related (P \u3c 0.001; r2 = 0.72) to grain yield in durum following oilseeds. Grain yield of durum following B. juncea was similar to durum following fallow and greater than durum following camelina or crambe. Durum following crambe tended to use N more inefficiently than durum following camelina, B. juncea, or fallow. Differences in yield and N use of durum and oilseeds varied among years, which underscores the need to further develop management tools to optimize durum-oilseed cropping systems in highly variable rainfall environments typical of the NGP

Efficacy of a Non-Hypercalcemic Vitamin-D2 Derived Anti-Cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model

BACKGROUND:Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING:Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein. SIGNIFICANCE:Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis

Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study

AbstractBackgroundThe optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists.MethodsAn online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy.ResultsThe response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive).DiscussionThe step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2–3 weeks of infected necrotizing pancreatitis

Wind erosion risk as an indicator of soil quality

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Saskatchewan soil enhancement project

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Tillage impact on carbon sequestration on rolling landscapes of farm fields in Saskatchewan

Non-Peer ReviewedLong term (10 to 25 years) rotation studies on the Canadian prairies have shown that conservation tillage and reduced fallow have, depending upon clay content and soil moisture deficits, sequestered from 0.3 to 0.7 Mg C ha-1yr-1 soil organic C (Liang et al., 1999a,b). However, since these studies were conducted on replicated and relative level research plots, it is questionable whether they reflect the reality of actual farm fields where landscapes and management practices often differ markedly from that on research plots. Therefore, the objective of this study was to quantify carbon sequestration as a function of conservation tillage on a range of typical soil-landscapes throughout Saskatchewan by comparing neighboring farmer’s fields with and without conservation tillage

The soil organic carbon story

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