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Glasses are ubiquitous in daily life and technology. However, the microscopic mechanisms generating this state of matter remain subject to debate: Glasses are considered either as merely hyperviscous liquids or as resulting from a genuine thermodynamic phase transition toward a rigid state. We show that third- and fifth-order susceptibilities provide a definite answer to this long-standing controversy. Performing the corresponding high-precision nonlinear dielectric experiments for supercooled glycerol and propylene carbonate, we find strong support for theories based on thermodynamic amorphous order. Moreover, when lowering temperature, we find that the growing transient domains are compact—that is, their fractal dimension df = 3. The glass transition may thus represent a class of critical phenomena different from canonical second-order phase transitions for which df < 3.

Purpose AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients. Patients and methods Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation. Results Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS ( p  = 0.016, HR = 0.63) and PFS ( p  = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed. Conclusion Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.

Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of β-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high β-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns.

BackgroundThe use of psychological screening instruments prior to bariatric surgery has been well established. However, there is currently no specific literature on psychological screening of candidates for reoperative bariatric surgery.MethodsThis study evaluated archival data for 40 women who were candidates for reoperative bariatric surgery and completed the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). Profile analysis examined differences between patient groups who did and did not undergo reoperative surgery. MMPI-2-RF profiles for reoperative patients then were compared to previous samples of preoperative and postoperative patients. Hierarchical linear modeling was used to predict BMI following reoperative surgery over a 12-month period based on MMPI-2-RF scales while controlling for age and initial BMI.ResultsProfile analysis results showed no significant differences on MMPI-2-RF scale scores between reoperative candidates who did and did not undergo a second surgery. With some minor differences attributed to minimization of symptoms, there were no systematic differences in MMPI-2-RF scale scores for reoperative surgery patients compared to preoperative and postoperative patient groups. BMI outcomes over a 12-month period showed that age and initial BMI were significantly better predictors than MMPI-2-RF scores.ConclusionsAdministration of MMPI-2-RF for reoperative bariatric surgery patients likely is equivalent to its typical use in preoperative screening. Only the MMPI-2-RF Disconstraint scale showed any relationship to BMI outcomes over time following reoperative surgery.

Objective: To analyze the clinical efficacy of 90 Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. Methods: Data from 19 pancreatic cancer patients (9 females/10 males) who had received 90 Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. Results: The median age at 90 Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after 90 Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at 90 Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. Conclusion: 90 Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities.

In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27–85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes ( n  = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) ( p  = 0.005) and between PD and stable disease (SD) ( p  = 0.042). CA 19-9 level slopes ( n  = 57; slopes = 127) also showed a significant difference between PD and PR ( p  = 0.002) and PD and SD ( p  = 0.058). Furthermore, CRP slopes ( n  = 62; slopes = 134) differed significantly between PD and PR ( p  = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in patients with mCRC receiving first-line chemotherapy. Further data analyses would be helpful to develop a predictive model for tumor response based on an early tumor marker increase or decrease.

Pancreatic cancer is a disease requiring urgent attention from governments and policymakers. Recently, a state of emergency has been declared for this cancer—being the fourth most common cause of cancer deaths in the European Union, it has the lowest survival rate of all common cancers. One of the major reasons pancreatic cancer is associated with such poor outcomes is because it is usually diagnosed at a late stage. Also, investment in research for effective targeted therapies is lacking. This is the perspective of a white paper developed by Digestive Cancers Europe, an umbrella organisation representing European patient organisations. It has been developed after consultation with pancreatic cancer patients, representatives of cancer patient organisations and leading pancreatic cancer healthcare professionals. The purpose of the paper is to highlight the key urgent unmet needs in pancreatic cancer from the patient perspective, ultimately with a view to improve patient care and outcomes in this very challenging disease.

We summarize current developments in the investigation of glassy matter using nonlinear dielectric spectroscopy. This work also provides a brief introduction into the phenomenology of the linear dielectric response of glass-forming materials and discusses the main mechanisms that can give rise to nonlinear dielectric response in this material class. Here we mainly concentrate on measurements of the conventional dielectric permittivity at high fields and the higher-order susceptibilities characterizing the 3-omega and 5-omega components of the dielectric response as performed in our group. Typical results on canonical glass-forming liquids and orientationally disordered plastic crystals are discussed, also treating the special case of supercooled monohydroxy alcohols.

We review the works devoted to third and fifth harmonic susceptibilities in glasses, namely \\(\\chi\\) (3) 3 and \\(\\chi\\) (5) 5. We explain why these nonlinear responses are especially well adapted to test whether or not some amorphous correlations develop upon cooling. We show that the experimental frequency and temperature dependences of \\(\\chi\\) (3) 3 and of \\(\\chi\\) (5) 5 have anomalous features, since their behavior is qualitatively different to that of an ideal gas, which is the high-temperature limit of a fluid. Most of the works have interpreted this anomalous behavior as reflecting the growth, upon cooling, of amorphously ordered domains, as predicted by the general framework of Bouchaud and Biroli (BB). We explain why most-if not all-of the challenging interpretations can be recast in a way which is consistent with that of Bouchaud and Biroli. Finally, the comparison of the anomalous features of \\(\\chi\\) (5) 5 and of \\(\\chi\\) (3) 3 shows that the amorphously ordered domains are compact, i.e., the fractal dimension d f is close to the dimension d of space. This suggests that the glass transition of molecular liquids corresponds to a new universality class of critical phenomena.

In this work we provide a thorough examination of the nonlinear dielectric properties of a succinonitrile-glutaronitrile mixture, representing one of the rare example of a plastic crystal with fragile glassy dynamics. The detected alteration of the complex dielectric permittivity under high fields can be explained considering the heterogeneous nature of glassy dynamics and a field-induced variation of entropy. While the first mechanism was also found in structural glass formers, the latter effect seems to be typical for plastic crystals. Morover, the third harmonic component of the dielectric susceptibility is reported, revealing a spectral shape as predicted for cooperative molecular dynamics. In accord with the fragile nature of the glass transition in this plastic crystal, we deduce a relatively strong temperature dependence of the number of correlated molecules, in contrast to the much weaker temperature dependence in plastic-crystalline cyclo-octanol, whose glass transition is of strong nature.