Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002-2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence. Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct KaplanMeier recurrence groups, thereby identifying patients more at-risk for recurrence. Such findings, achievable by biopsy or prostatectomy tissue measurement, could inform treatment strategies. Metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically-benign tissues in cancer environments.The utility of the serum prostate specific antigen (PSA) screening test is now well established, both by its capacity to reveal early-stage disease and its discovery of almost all newly-detected prostate cancers 1-3 . However, despite being prostate-specific, PSA testing is not cancer-specific. Current medical imaging detects 44-87% 4 of clinically significant cancers but remains challenged by small lesions. For this reason, prostate cancer (PCa) diagnoses are still only positively confirmed by prostate transrectal biopsies, performed after an elevated PSA result. After a positive biopsy, an initial cancer grade is assigned according to histological analysis of the biopsy cores; this grade will help determine whether the prostate should be surgically removed by prostatectomy or the patient should enter active surveillance. If a prostatectomy is performed, histological examination of the entire prostate will determine the pathological stage of the disease. With this information, follow-up therapies can be recommended, if warranted.Statistics on prostate cancer's natural history suggest that >70% of patients diagnosed after PSA screening are likely to experience an indolent disease course that little impacts their well-being. About 17% of these newly PSA-diagnosed patients, however, will confront an aggressive prostate cancer that significantly impairs function

Low-dose CT has shown promise in detecting early stage lung cancer. However, concerns about the adverse health effects of radiation and high cost prevent its use as a population-wide screening tool. Effective and feasible screening methods to triage suspicious patients to CT are needed. We investigated human lung cancer metabolomics from 93 paired tissue-serum samples with magnetic resonance spectroscopy and identified tissue and serum metabolomic markers that can differentiate cancer types and stages. Most interestingly, we identified serum metabolomic profiles that can predict patient overall survival for all cases (p = 0.0076), and more importantly for Stage I cases alone (n = 58, p = 0.0100), a prediction which is significant for treatment strategies but currently cannot be achieved by any clinical method. Prolonged survival is associated with relative overexpression of glutamine, valine, and glycine, and relative suppression of glutamate and lipids in serum.

Summary Delirium occurs commonly following major non‐cardiac and cardiac surgery and is associated with: postoperative mortality; postoperative neurocognitive dysfunction; increased length of hospital stay; and major postoperative complications and morbidity. The aim of this study was to investigate the effect of peri‐operative administration of dexmedetomidine on the incidence of postoperative delirium in non‐cardiac and cardiac surgical patients. In this randomised, double‐blind placebo‐controlled trial we included 63 patients aged ≥ 60 years undergoing major open abdominal surgery or coronary artery bypass graft surgery with cardiopulmonary bypass. The primary outcome was the incidence of postoperative delirium, as screened for with the Confusion Assessment Method. Delirium assessment was performed twice daily until postoperative day 5, at the time of discharge from hospital or until postoperative day 14. We found that dexmedetomidine was associated with a reduced incidence of postoperative delirium within the first 5 postoperative days, 43.8% vs. 17.9%, p = 0.038. Severity of delirium, screened with the Intensive Care Delirium Screening Checklist, was comparable in both groups, with a mean maximum score of 1.54 vs. 1.68, p = 0.767. No patients in the dexmedetomidine group died while five (15.6%) patients in the placebo group died, p = 0.029. For patients aged ≥ 60 years undergoing major cardiac or non‐cardiac surgery, we conclude that the peri‐operative administration of dexmedetomidine is associated with a lower incidence of postoperative delirium.

Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after surgery (pod5). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5. Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.

BACKGROUND Annual PSA tests have led to a significant increase in the number of prostate cancer (PCa) cases diagnosed. This increased incidence has led to overtreatment of many patients, as current pathology often cannot distinguish latent from aggressive PCa. Studies have shown that the depletion of zinc in prostate cells correlated with cell-line growth rates, and may therefore relate to the progression of PCa. Furthermore, as zinc is normally an inhibitor of citrate oxidation, the reduction of zinc in PCa may cause a decrease in citrate secretion levels in the glandular epithelia of PCa patients. METHODS Using high-resolution magic angle spinning proton magnetic resonance spectroscopy followed by quantitative histopathology, we investigate unit histo-benign prostate epithelial citrate concentrations in intact tissue samples obtained from 18 patients with pre-surgical PSA values less than 20 ng/ml. Using these data, we evaluate correlations between citrate concentrations and PSA velocities, densities and blood percent-free PSA. RESULTS We observe different linear patterns between citrate concentrations and histo-benign glandular epithelia from patients of different PSA velocities. More importantly, we obtain a significant correlation between PSA velocity, density and percent-free PSA, and citrate concentrations in unit volume of histo-benign epithelial glands of the peripheral zone. CONCLUSIONS Low levels of citrate in unit volume represent rapidly increasing PSA values, and, therefore, may be used as an indicator of fast-growing PCa. Thus, tissue samples obtained at the time of biopsy may be evaluated for their citrate concentrations for the prediction of PCa growth rates, allowing for the implementation of alternative treatment options and reducing overtreatment.

Introduction: Elderly patients suffering from gastrointestinal malignancies are particularly prone to perioperative complications. Elderly patients often present with reduced physiological reserves, and comorbidities can limit treatment options and promote complications. Surgeons and anesthesiologists must be aware of strategies required to deal with this vulnerable subgroup. Methods: We provide a brief review of current and emerging perioperative strategies for the treatment of elderly patients with gastrointestinal malignancies and frequent comorbidities. Results: Especially in combination with advanced age, the effects of malignancies can be devastating, bringing new health challenges, exacerbating preexisting conditions, and exerting severe psychological strain. An interdisciplinary assessment and process planning provide an ideal setting to identify and prevent potential complications, especially in regards to frailty and cardiovascular risk. In addition, important perioperative considerations are presented, such as malnutrition, fasting, intraoperative neuromonitoring, and hemodynamic control, as well as postoperative early mobilization, pain, and delirium management. Conclusion: The decisions and interventions made in the perioperative stage can positively influence many intra- and postoperative factors, significantly improving the chances of successful treatment of elderly cancer patients. Appropriate management can help prevent or mitigate complications, secure a quick recovery, and improve short- and long-term outcomes.

Background Monocytic human leukocyte antigen D related (mHLA-DR) is essential for antigen-presentation. Downregulation of mHLA-DR emerged as a general biomarker of impaired immunity seen in patients with sepsis and pneumonia and after major surgery. Influencing factors of mHLA-DR such as age, overweight, diabetes, smoking, and gender remain unclear. Methods We analyzed 20 patients after esophageal or pancreatic resection of a prospective, randomized, placebo-controlled, double-blind trial (placebo group). mHLA-DR was determined from day of surgery (od) until postoperative day (pod) 5. Statistical analyses were performed using multivariate generalized estimating equation analyses (GEE), nonparametric multivariate analysis of longitudinal data, and univariate post hoc nonparametric Mann–Whitney tests. Results In GEE, smoking and gender were confirmed as significant influencing factors over time. Univariate analyses of mHLA-DR between smokers and nonsmokers showed lower preoperative levels (p = 0.010) and a trend towards lower levels on pod5 (p = 0.056) in smokers. Lower mHLA-DR was seen in men on pod3 (p = 0.038) and on pod5 (p = 0.026). Overweight patients (BMI > 25 kg/m2) had lower levels of mHLA-DR on pod3 (p = 0.039) and pod4 (p = 0.047). Conclusion Smoking is an important influencing factor on pre- and postoperative immune function while postoperative immune function was influenced by gender and overweight. Clinical trial registered with ISRCTN27114642.

BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) can be used as a potent stimulator for immune suppressed patients as defined by a decrease of human leukocyte antigen-D related expression on monocytes (mHLA-DR) after surgery. However, the exact role of GM-CSF on monocytic and T cell function is unclear. METHODS: In this retrospective randomized controlled trial (RCT) subgroup analysis, monocytic respectively T cell function and T cell subspecies of 20 immune suppressed (i.e. mHLA-DR levels below 10,000 monoclonal antibodies (mAb) per cell at the first day after surgery) patients after esophageal or pancreatic resection were analyzed. Each 10 patients received either GM-CSF (250 μg/m²/d) or placebo for a maximum of three consecutive days if mHLA-DR levels remained below 10,000 mAb per cell. mHLA-DR and further parameters of immune function were measured preoperatively (od) until day 5 after surgery (pod5). Statistical analyses were performed using nonparametric statistical procedures. RESULTS: In multivariate analysis, mHLA-DR significantly differed between the groups (p < 0.001). mHLA-DR was increased on pod2 (p < 0.001) and pod3 (p = 0.002) after GM-CSF application. Tumor necrosis factor-α (TNF-α) release of lipopolysaccharide (LPS) stimulated monocytes multivariately significantly differed between the groups (p < 0.008) and was increased in the GM-CSF group on pod2 (p < 0.001) and pod3 (p = 0.046). Th17/regulatory T (Treg) cell ratio was higher after GM-CSF treatment on pod2 (p = 0.041). No differences were seen in lymphocytes and T helper cell (Th)1/Th2 specific cytokine production after T cell stimulation with Concanavalin (Con) A between the groups. CONCLUSIONS: Postoperative application of GM-CSF significantly enhanced qualitative monocytic function by increased mHLA-DR and TNF-α release after LPS stimulation and apparently enhanced Th17/Treg ratio.Clinical trial registered with www.controlled-trials.com (ISRCTN27114642) 05 December 2008.