Colorectal liver metastases: Current management and future perspectives.

The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation

Evaluation of magnetic resonance imaging for bladder cancer detection following transurethral resection of bladder tumour (TURBT)

Purpose To evaluate the performance of MRI for detection of bladder cancer following transurethral resection of bladder tumour (TURBT). Methods This single-centre retrospective study included forty-one consecutive patients with bladder cancer who underwent bladder MRI after TURBT. Two uroradiologists retrospectively assessed the presence of tumour using bladder MRI with and without DWI (diffusion weighted imaging) using a five-point Likert scale. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated and inter-reader agreement was assessed. Histopathology was used as the reference standard. Results 24 out of 41 patients (58.5%) had no residual tumour or Tis (carcinoma in situ) after TURBT. Sensitivity, specificity, PPV and NPV for detection of tumour using T1WI (T1-weighted imaging) and T2WI (T2-weighted imaging) was 50.0%, 54.6%, 21.1%, and 81.8%, respectively and for T1WI, T2WI and DWI combined was 100%, 76.5%, 50.0% and 100%, respectively. Overestimation of tumour was more common than underestimation. MRI showed high accuracy for patients in whom there was no residual tumour (78.9%). Inter-reader agreement for tumour detection improved from fair (κ= 0.54) to moderate (κ=0.70) when DWI was included. Conclusion Non-contrast MRI with DWI showed high sensitivity and relatively high specificity for detection of residual tumour after TURBT. Inter-reader agreement improved from fair to moderate with the addition of DWI. MRI can be useful after TURBT in order to guide further management

Renin-angiotensin system inhibition in advanced chronic kidney disease

Renin-angiotensin system (RAS) inhibitors - including angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) - slow the progression of mild or moderate chronic kidney disease. However, the results of some studies have suggested that the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline. In this multicenter, open-label trial, we randomly assigned patients with advanced and progressive chronic kidney disease (eGFR, <30 ml per minute per 1.73 m of body-surface area) either to discontinue or to continue therapy with RAS inhibitors. The primary outcome was the eGFR at 3 years; eGFR values that were obtained after the initiation of renal-replacement therapy were excluded. Secondary outcomes included the development of end-stage kidney disease (ESKD); a composite of a decrease of more than 50% in the eGFR or the initiation of renal-replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria. At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22). Among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR

Isoniazid hair concentrations in children with tuberculosis: a proof of concept study

Assessing treatment adherence and quantifying tuberculosis drug exposure among children is challenging. We undertook a “proof of concept” study to assess the drug concentrations of isoniazid in hair as a therapeutic drug monitoring tool. Children <12 years of age initiated on thrice-weekly treatment including isoniazid (10 mg/kg) for newly diagnosed tuberculosis were enrolled. Isoniazid concentrations in hair were measured using liquid chromatography-tandem mass spectrometry at 1, 2, 4 and 6 months after tuberculosis treatment initiation. We found that isoniazid hair concentrations in all children on thrice weekly isoniazid were detectable and displayed variability across a dynamic range

Venous thromboembolism risk and prophylaxis in hospitalised medically ill patients The ENDORSE Global Survey

Limited data are available regarding the risk for venous thromboembolism (VIE) and VIE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VIE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VIE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active noninfectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40-45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VIE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VIE risk and providing prophylaxis to hospitalised medical patients

Venous Thromboembolism Risk and Prophylaxis in the Acute Care Hospital Setting (ENDORSE Survey) Findings in Surgical Patients

Objective: To evaluate venous thromboembolism (VTE) risk in patients who underwent a major operation, including the use of, and factors influencing, American College of Chest Physicians-recommended types of VTE prophylaxis