Pancreatic ductal adenocarcinoma (PDAC) is one of the five most lethal malignancies worldwide and survival has not improved substantially in the past 30 years. Desmoplasia (abundant fibrotic stroma) is a typical feature of PDAC in humans, and stromal activation commonly starts around precancerous lesions. It is becoming clear that this stromal tissue is not a bystander in disease progression. Cancer-stroma interactions effect tumorigenesis, angiogenesis, therapy resistance and possibly the metastatic spread of tumour cells. Therefore, targeting the tumour stroma, in combination with chemotherapy, is a promising new option for the treatment of PDAC. In this Review, we focus on four issues. First, how can stromal activity be used to detect early steps of pancreatic carcinogenesis? Second, what is the effect of perpetual pancreatic stellate cell activity on angiogenesis and tissue perfusion? Third, what are the (experimental) antifibrotic therapy options in PDAC? Fourth, what lessons can be learned from Langton's Ant (a simple mathematical model) regarding the unpredictability of genetically engineered mouse models?

BackgroundThe current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock.MethodsIn a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90–110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002–2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions.Findings9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR  = 0.85, 95%CI 0.81–0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94–1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78–0.93) compared to 22.6% (SMR 1.03, CI95% 0.94–1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92–1.06) compared to 54.9% (SMR 1.10, CI95% 1.02–1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60–0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52–0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock.ConclusionsWBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.

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Purpose:We prospectively evaluated the predictive value of positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) for in vivo testing of chemosensitivity in locally advanced gastric cancer using an a priori definition of metabolic response (a decrease of >35% of the standarduptake value).The goalof the study was the definitionof biologically differentgroups of patients prior to or early during induction therapy, with special emphasis on FDGnon^avid tumors. Experimental Design: Based on our data, which was published in 2003, at least 36 patients with metabolic response or FDG non^avid tumors had to be recruited for an analysis of the group of FDG non^avid tumors with sufficient statistical power. Seventy-one patients (32 metabolic nonresponders, 17 metabolic responders, and 22 patients with FDG non^avid tumors) underwent FDG-PET at baseline. In FDG-avid tumors, FDG-PET was repeated 14 days after the initiation of chemotherapy. Results: Metabolic responders (17 of 49) showed a high histopathologic response rate (69%) and a favorable prognosis (median survival not reached), whereas metabolic nonresponders (32 of 49) had a poor prognosis (median survival, 24.1 months) and showed a histopathologic response in 17%. The histopathologic response rate (24%) for FDG-PET non^avid patients showed no significant difference compared with FDG-avid nonresponders (P = 0.72). Survival of FDG non^avid patients was 36.7 months (not significantly different from FDG-avid nonresponders, 24.1months, P = 0.46). Conclusion: In locally advanced gastric cancer, three different metabolic groups exist. Response and survival was predicted by PET in FDG-avid tumors. Metabolic response assessment was not possible in FDG non^avid tumors; however, due to unfavorable outcome, therapy modification might also be considered in FDG non^avid tumors.Recently, a randomized phase III study in patients with operable gastric or lower esophageal adenocarcinoma was published by Cunningham et al., demonstrating improved overall and progression-free survival following perioperative chemotherapy compared with surgery alone (1).However, only 30% to 40% of patients showed a measurable clinical or histopathologic response after neoadjuvant treatment (2 -6). Therefore, it would be important to identify patients who do not respond to chemotherapy early in the course of treatment, or even prior to treatment, in order to avoid ineffective therapy with its associated side effects and costs.Current imaging modalities or molecular markers cannot reliably predict therapy response prior to or early in the course of the treatment-the time when this information is most important (7,8). In contrast, positron emission tomography (PET) imaging after 2 weeks of chemotherapy is significantly correlated with histopathologic regression and prognosis in patients with adenocarcinoma of the esophagogastric junction (AEG) I and II (5, 6). Interestingly, approximately one third of patients with gastric cancer, even with locally advanced tumors, initially hav...