The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines ® Insights highlight important changes in the NCCN Guidelines ® recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed. The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN ®) makes no representation or warranties of any kind regarding the content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their applications or use in any way. The full and most current version of these NCCN Guidelines is available at NCCN.org.

Objective: The lack of readily available branched and fenestrated endovascular aneurysm repair (EVAR) options has created an opportunity for creative deployment of endograft components to treat juxtarenal aneurysms. We present our early experience with "snorkel" or "chimney" techniques in the endovascular management of complex aortic aneurysms. Methods: We retrospectively reviewed planned snorkel procedures for juxtarenal aneurysms performed from September 2009 to August 2011. Our standardized technique included axillary or brachial cutdown for delivery of covered snorkel stents and mostly percutaneous femoral access for the main body endograft. Results: Fifty-six snorkel grafts were successfully placed in 28 consecutive patients (mean age, 75 years) with juxtarenal aneurysms. Mean aneurysm size was 64.8 mm (range, 53-87 mm). The snorkel configuration extended the proximal seal zone from an unsuitable infrarenal neck for standard EVAR (median diameter, 33.5 mm; length, 0.0 mm) to a median neck diameter of 24.5 mm and length of 18.0 mm. Five patients had unilateral renal snorkels, 17 had bilateral renal snorkels, and six had celiac/superior mesenteric artery/renal combinations. Technical success of snorkel placements was 98.2%, with loss of wire access leading to one renal stent deployment failure. Thirty-day mortality was 7.1%: one patient was readmitted 1 week postoperatively with pneumonia and died of sepsis; one patient died at 1 week of a right hemispheric stroke. Other major complications included perinephric hematomas, 7.1%; permanent hemodialysis, 3.6%; iliac artery injury requiring endoconduit placement, 3.6%; and brachial plexus nerve injury, 3.6%. Cardiac complications included self-limited arrhythmias (14.3%) and one non-Q-wave myocardial infarction (3.6%), with all recovering without coronary intervention. Mean follow-up was 10.7 months (range, 3-25 months). One patient died of nonaneurysmalrelated causes at 3 months (89.3% survival). Postoperative imaging revealed one renal snorkel graft occlusion occurring at 3 months (98.2% overall primary patency). Seven (25%) early endoleaks were noted on the first follow-up computed tomography angiography: two type I, three type II, and two type III (25%), leading to one secondary intervention (3.6%) with bridging cuff placement (type III). The small type Ia endoleaks and other type III endoleak resolved at the 6-month scan. Mean sac regression at the latest follow-up was 7.3 mm. No aneurysm has enlarged on postoperative imaging. Conclusions: Early success with the snorkel technique for juxtarenal aneurysms has made it our procedure of choice for complex short-neck to no-neck EVAR. Although long-term follow-up is needed, the flexibility of the snorkel technique and lack of requirement for custom-built devices may make this approach more attractive than branched or fenestrated stent grafts. ( J Vasc Surg 2012;55:935-46.)

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

A.J. performed transthoracic injections. G.A. performed a portion of the CT scans. M.M. and S.T.B. performed IHC staining and analyzed data. M.M. J.T.L. and A.J. performed in vitro 18 FBnTP uptake assays. M.M. did TMRE staining and western blots. M.C.F is a board-certified anatomic pathologist who performed the pathological analysis. L.S. and O.S. performed and guided respirometry experiments. S.S., C.M.W., A.G. and T.H. performed radio-tracer synthesis. D.D. and C.K. performed biochemical analysis of mitochondria. E.S. and H.C. performed metabolic analysis of lung tumors. S.M.D. contributed resources and critical feedback on the project. Data availability Source data for Western blots are provided with the paper as Supplementary Figure 1. Source data for Figures 1b-d; Figures 2d-g; Figures 3b, 3d, 3e; ED Figures 3c-e; ED Figures 4c, 4d; ED Figure 9a are provided with the paper. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Cancer cells exhibit increased use of nutrients including glucose and glutamine to support the bioenergetic and biosynthetic demands of proliferation. We tested the small molecule inhibitor of glutaminase CB-839 in combination with erlotinib on EGFR mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMPK pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-Glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following CB-839 + erlotinib treatment. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy.

Structured endovascular skills assessment correlates well with prior procedural experience within a high-fidelity simulation environment. In addition to improving endovascular training, simulators may prove useful in determining procedural competency and credentialing standards for endovascular surgeons.

Monitoring genetically altered T cells is an important component of adoptive T cell therapy in patients, and the ability to visualize their trafficking/targeting, proliferation/expansion, and retention/death using highly sensitive reporter systems that do not induce an immunologic response would provide useful information. Therefore, we focused on human reporter gene systems that have the potential for translation to clinical studies. The objective of the in vivo imaging studies was to determine the minimum number of T cells that could be visualized with the different nuclear reporter systems. We determined the imaging sensitivity (lower limit of T cell detection) of each reporter using appropriate radiolabeled probes for PET or SPECT imaging. Methods Human T cells were transduced with retroviral vectors encoding for the human norepinephrine transporter (hNET), human sodiumiodide symporter (hNIS), a human deoxycytidine kinase double mutant (hdCKDM), and herpes simplex virus type 1 thymidine kinase (hsvTK) reporter genes. After viability and growth were assessed, 105 to 3 × 106 reporter T cells were injected subcutaneously on the shoulder area. The corresponding radiolabeled probe was injected intravenously 30 min later, followed by sequential PET or SPECT imaging. Radioactivity at the T cell injection sites and in the thigh (back-ground) was measured. Results The viability and growth of experimental cells were unaffected by transduction. The hNET/meta-18F-fluorobenzylguanidine (18F-MFBG) reporter system could detect less than 1 × 105 T cells because of its high uptake in the transduced T cells and low background activity. The hNIS/124I-iodide reporter system could detect approximately 1 × 106 T cells; 124I-iodide uptake at the T cell injection site was time-dependent and associated with high background. The hdCKDM/2′-18F-fluoro-5-ethyl-1-β-D-arabinofuranosyluracil (18F-FEAU) and hsvTK/18F-FEAU reporter systems detected approximately 3 × 105 T cells, respectively. 18F-FEAU was a more efficient probe (higher uptake, lower background) than 124I-1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil for both hdCKDM and hsvTK. Conclusion A comparison of different reporter gene–reporter probe systems for imaging of T cell number was performed, and the hNET/18F-MFBG PET reporter system was found to be the most sensitive and capable of detecting approximately 35–40 × 103 T cells at the site of T cell injection in the animal model.