Study protocol: HepaT1ca - an observational clinical cohort study to quantify liver health in surgical candidates for liver malignancies.

Background Accurate assessment of liver health prior to undertaking resectional liver surgery or chemoembolisation for primary and secondary cancers is essential for patient safety and optimal outcomes. LiverMultiScan™, an MRI-based technology, non-invasively quantifies hepatic fibroinflammatory disease, steatosis and iron content. We hypothesise that LiverMultiScan™can quantify liver health prior to surgery and inform the risk assessment for patients considering liver surgery or chemoembolization and seek to evaluate this technology in an operational environment. Methods/Design HepaT1ca is an observational cohort study in two tertiary-referral liver surgery centres in the United Kingdom. The primary outcome is correlation between the pre-operative liver health assessment score (Hepatica score - calculated by weighting future remnant liver volume by liver inflammation and fibrosis (LIF) score) and the post-operative liver function composite integer-based risk (Hyder-Pawlik) score. With ethical approval and fully-informed consent, individuals considering liver surgery for primary or secondary cancer will undergo clinical assessment, blood sampling, and LiverMultiScan™multiparametric MRI before and after surgical liver resection or TACE. In nested cohorts of individuals undergoing chemotherapy prior to surgery, or those undergoing portal vein embolization (PVE) as an adjunct to surgery, an additional testing session prior to commencement of treatment will occur. Tissue will be examined histologically and by immunohistochemistry. Pre-operative liver health assessment scores and the post-operative risk scores will be correlated to define the ability of LiverMultiScan™to predict the risk of post-operative morbidity and mortality. Because technology performance in this setting is unknown, a pragmatic sample size will be used. For the primary outcome, n = 200 for the main cohort will allow detection of a minimum correlation coefficient of 0.2 with 5% significance and power of 80%. Discussion This study will refine the technology and clinical application of multiparametric MRI (including LiverMultiScan™), to quantify pre-existing liver health and predict post-intervention outcomes following liver resection. If successful, this study will advance the technology and support the use of multiparametric MRI as part of an enhanced pre-operative assessment to improve patient safety and to personalise operative risk assessment of liver surgery/non-surgical intervention

Genome-Wide Modeling of Transcription Preinitiation Complex Disassembly Mechanisms using ChIP-chip Data

Apparent occupancy levels of proteins bound to DNA in vivo can now be routinely measured on a genomic scale. A challenge in relating these occupancy levels to assembly mechanisms that are defined with biochemically isolated components lies in the veracity of assumptions made regarding the in vivo system. Assumptions regarding behavior of molecules in vivo can neither be proven true nor false, and thus is necessarily subjective. Nevertheless, within those confines, connecting in vivo protein-DNA interaction observations with defined biochemical mechanisms is an important step towards fully defining and understanding assembly/disassembly mechanisms in vivo. To this end, we have developed a computational program PathCom that models in vivo protein-DNA occupancy data as biochemical mechanisms under the assumption that occupancy levels can be related to binding duration and explicitly defined assembly/disassembly reactions. We exemplify the process with the assembly of the general transcription factors (TBP, TFIIB, TFIIE, TFIIF, TFIIH, and RNA polymerase II) at the genes of the budding yeast Saccharomyces. Within the assumption inherent in the system our modeling suggests that TBP occupancy at promoters is rather transient compared to other general factors, despite the importance of TBP in nucleating assembly of the preinitiation complex. PathCom is suitable for modeling any assembly/disassembly pathway, given that all the proteins (or species) come together to form a complex

The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis

OBJECTIVE: To meta-analyse the diagnostic accuracy of US, CT, MRI and (1)H-MRS for the evaluation of hepatic steatosis. METHODS: From a comprehensive literature search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles were selected that investigated the diagnostic performance imaging techniques for evaluating hepatic steatosis with histopathology as the reference standard. Cut-off values for the presence of steatosis on liver biopsy were subdivided into four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30 and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and specificity were calculated. The natural-logarithm of the diagnostic odds ratio (lnDOR) was used as a single indicator of test performance. RESULTS: 46 articles were included. Mean sensitivity estimates for subgroups were 73.3-90.5% (US), 46.1-72.0% (CT), 82.0-97.4% (MRI) and 72.7-88.5% ((1)H-MRS). Mean specificity ranges were 69.6-85.2% (US), 88.1-94.6% (CT), 76.1-95.3% (MRI) and 92.0-95.7% ((1)H-MRS). Overall performance (lnDOR) of MRI and (1)H-MRS was better than that for US and CT for all subgroups, with significant differences in groups 1 and 2. CONCLUSION: MRI and (1)H-MRS can be considered techniques of choice for accurate evaluation of hepatic steatosi

Psychological factors and preferences for communicating prognosis in esophageal cancer patients

Objective: Discussing prognosis is often confronting and complex for cancer patients. This study investigates bow patients' psychological characteristics relate to their preferences concerning the disclosure of prognosis. Methods: One hundred and seventy-six esophageal cancer patients participated in the study. They had undergone esophagectomy within the past 28 months and did not have evidence of cancer recurrence. Patients completed a questionnaire eliciting their preferences for prognostic information. Sociodemographic characteristics, involvement preferences, anxiety, depression, fear of recurrence, striving for quality of life (QOL) or quantity of life and trust in physicians were explored as predictors for (a) wanting to be informed about prognosis and (b) the initiation of discussion about prognosis. Results: Patients wanting all prognostic information had more fear for the disease to recur (p < 0.05) and were inclined to be more actively involved during consultation (p < 0.001). Post hoc analyses showed that patients with worse QOL scores reported more fear of recurrence. Anxiety, depression, trust and tendency to strive for QOL or quantity of life were not related to preferences concerning prognostic information. Conclusions: The more fear patients have for esophageal cancer to recur, the more information they want about prognosis. Thus, patient's fear for recurrent disease is not a reason for withholding prognostic information. Results also suggest that there is no harm in asking patients what information they want. Copyright (C) 2009 John Wiley & Sons, Ltd

Patient Preferences for the Disclosure of Prognosis After Esophagectomy for Cancer with Curative Intent

Introduction: The aim of this study was to determine the preferences for content, style, and format of prognostic information of patients after potentially curative esophagectomy for cancer and to explore predictors of these preferences. Patients and Methods: This multicenter study included a consecutive series of patients who underwent surgical resection for cancer in the past 2 years and who did not have evidence of cancer recurrence. A questionnaire was used to elicit patient preferences for the content, style, and format of prognostic information. Sociodemographic characteristics, clinicopathological factors, and quality of life (EORTC QLQ-30 and OES18) were explored as predictors for certain preferences. Results: Of the 204 eligible patients, 176 patients (86%) returned the questionnaire. The majority of patients desired prognostic information. Information preferences declined when information became more specific and more negative. Married patients and higher-educated patients were more likely to want all prognostic information. The majority of patients wanted their specialist to start the discussion about prognosis. However, a significant proportion of these patients wanted their specialist to first ask if they want to have prognostic information. The percentage of patients wanted a realistic and individualistic approach was 97%. Words and numbers were preferred over visual presentations. Conclusion: After potentially curative esophagectomy for cancer, the majority of patients want detailed prognostic information and want their specialist to begin the prognostic discussion. Patients prefer their doctor to be realistic; words and numbers are preferred over figures and graphs