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

The value of source data verification in a cancer clinical trial

Background Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial. Methods Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those based on data without SDV. Overall survival (OS) and Progression-free survival (PFS) were compared using Kaplan-Meier curves, log-rank tests and Cox models. Tumour response classifications and comparative treatment Odds Ratios (ORs) for the outcome objective response rate, and number of Serious Adverse Events (SAEs) were compared. OS estimates based on SDV data were compared against estimates obtained from centrally monitored data. Findings Data discrepancies were identified between different monitoring procedures for the majority of variables examined, with some variation in discrepancy rates. There were no systematic patterns to discrepancies and their impact was negligible on OS, the primary outcome of the trial (HR (95% CI): 1.18(0.99 to 1.41), p = 0.064 with 100% SDV; 1.18(0.99 to 1.42), p = 0.068 without SDV; 1.18(0.99 to 1.40), p = 0.073 with central monitoring). Results were similar for PFS. More extreme discrepancies were found for the subjective outcome overall objective response (OR (95% CI): 1.67(1.04 to 2.68), p = 0.03 with 100% SDV; 2.45(1.49 to 4.04), p = 0.0003 without any SDV) which was mostly due to differing CT scans. Interpretation Quality assurance methods used in clinical trials should be informed by empirical evidence. In this empirical comparison, SDV was expensive and identified random errors that made little impact on results and clinical conclusions of the trial. Central monitoring using an external data source was a more efficient approach for the primary outcome of OS. For the subjective outcome objective response, an independent blinded review committee and tracking system to monitor missing scan data could be more efficient than SDV

Management and Outcome of 64 Patients with Pancreatic Serous Cystic Neoplasms

Background: The optimal management approach to pancreatic serous cystic neoplasms (SCNs) is still evolving. Methods: Consecutive patients with SCN managed at the Liverpool Pancreas Cancer Centre between 2000 and 2013 were retrospectively reviewed. Results: There were 64 patients consisting of 39 women (60.9%) and 25 men (39.1%). Forty-seven patients (73.4%) had surgical removal and 17 (26.6%) were observed. The possibility of a non-SCN malignancy was the predominant indication for resection in 27 (57.4%) patients. Postoperative morbidity occurred in 26 (55.3%) patients with 2 (4.3%) deaths. An increased risk of resection was associated with patient's age (p = 0.011), diagnosis before 2009 (p < 0.001), pain (p = 0.043), possibility of cancer (p = 0.009) and a solid SCN component on imaging (p = 0.002). Independent factors associated with resection were a diagnosis before 2009 (p = 0.005) and a solid SCN component (p < 0.001). Independent factors associated with shorter time to surgical resection were persistent pain (p = 0.003) and a solid SCN component (p = 0.007). Conclusion: There was a reduction in the proportion of resections with the application of an observe-only policy for asymptomatic patients with more definite features of SCN. Improved criteria are still required in the remainder of patients with uncertain features of SCN in deciding for intervention or surveillance

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

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

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