The Prognostic Significance of the Preoperative Full Blood Count after Resection of Colorectal Liver Metastases

Introduction. Increased preoperative platelet and neutrophil counts are risk factors for decreased survival in several different malignancies. Our aim was to investigate the relationship between overall or disease-free survival after resection of CRLM and the preoperative haematological parameters. Methods. We reviewed a cohort of 140 patients who underwent resection of CRLM with curative intent, utilising prospectively maintained databases. Patient demographics, operative details, FBC, CRP, INR, histopathology results, and survival data were examined. Kaplan-Meier survival and Cox regression analyses were used to determine the impact of all variables on survival. Results. 140 patients (96 males) with a median age of 67 years (range 33–82 years) underwent resection of CRLM. A significant correlation was exhibited between preoperative platelet count and neutrophil count (rho = 0.186, P = .028). When modelled as continuous covariates in a Cox regression hazards, an increased preoperative platelet (P = .02) and neutrophil counts (P ≤ .001) were significantly associated with overall survival. Of the haematological parameters assessed only preoperative platelet count showed a strong trend of association with disease free survival; however this failed to reach statistical significance (P = .076). Conclusions. Increased preoperative platelet and neutrophil counts are independent risk factors for decreased survival in patients undergoing resection of CRLM in our series of patients. These findings require validation in larger studies to determine their relationship with survival. Further research into the role of these cell types in tumour progression, particularly in the development and inhibition of angiogenesis, is warranted

What Is the Best Way to Identify Malignant Transformation Within Pancreatic IPMN: A Systematic Review and Meta-Analyses

OBJECTIVES: Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN. METHODS: Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed. RESULTS: A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906. CONCLUSIONS: PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs

Signature Change in Noncommutative FRW Cosmology

The conditions for which the no boundary proposal may have a classical realization of a continuous change of signature, are investigated for a cosmological model described by FRW metric coupled with a self interacting scalar field, having a noncommutative phase space of dynamical variables. The model is then quantized and a good correspondence is shown between the classical and quantum cosmology indicating that the noncommutativity does not destruct the classical-quantum correspondence. It is also shown that the quantum cosmology supports a signature transition where the bare cosmological constant takes a vast continuous spectrum of negative values. The bounds of bare cosmological constant are limited by the values of noncommutative parameters. Moreover, it turns out that the physical parameters are constrained by the noncommutativity parametres.Comment: 15 pages, 4 figures, Minor revision, references adde

Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes

BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK

PANasta Trial; Cattell Warren versus Blumgart techniques of panreatico-jejunostomy following pancreato-duodenectomy: Study protocol for a randomized controlled trial

PANasta operative manual. (PDF 520 kb

Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials

The ESPAC-1, ESPAC-1 plus, and early ESPAC-3(v1) results (458 randomized patients; 364 deaths) were used to estimate the effectiveness of adjuvant 5FU/FA vs resection alone for pancreatic cancer using meta-analysis. The pooled hazard ratio of 0.70 (95% CI=0.55–0.88) P=0.003, and the median survival of 23.2 (95% CI=20.1–26.5) months with 5FU/FA vs 16.8 (95% CI=14.3–19.2) months with resection alone supports the use of adjuvant 5FU/FA in pancreatic cancer

FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer

Pancreatic cancer has one of the highest mortalities among all malignancies and there is an urgent need for new therapy. This might be achieved by resolving the detailed biological mechanism, and in this study we examined how pancreatic cancer cells develop aggressive properties by focusing on signalling through the fibroblast growth factor (FGF)10 and FGF receptor (FGFR)2, which play important roles in pancreatic organogenesis. Immunostaining of pancreatic cancer tissues showed that FGFR2 was expressed in cancer cells, whereas FGF10 was expressed in stromal cells surrounding the cancer cells. Patients with high FGFR2 expression in cancer cells had a shorter survival time compared to those with low FGFR2 expression. Fibroblast growth factor 10 induced cell migration and invasion of CFPAC-1 and AsPC-1 pancreatic cancer cells through interaction with FGFR2-IIIb, a specific isoform of FGFR2. Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-β1, and increased secretion of TGF-β1 protein from these cell lines. These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer

Optimal Duration and Timing of Adjuvant Chemotherapy After Definitive Surgery for Ductal Adenocarcinoma of the Pancreas: Ongoing Lessons From the ESPAC-3 Study

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Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). Conclusion: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study. Keywords: Calpain, Calpastatin, Pancreas, Ampulla, Bile duct, Cance