A Rationale for Safe Ventilation with Inhalation Injury: An Editorial Review.

Lung injury from smoke inhalation manifests as airway and parenchymal damage, at times leading to the acute respiratory distress syndrome. From the beginning of this millennium, the approach to mechanical ventilation in the patient with ARDS was based on reduction of tidal volume to 6 milliliters/kilogram of ideal body weight, maintaining a ceiling of plateau pressure, and titration of driving pressure (plateau pressure minus PEEP). Beyond these broad constraints, there is little specification for the mechanics of ventilator settings, consideration of the metabolic impact of the disease process on the patient, or interaction of patient disease and ventilator settings. Various studies suggest that inhomogeneity of lung injury, which increases the risk of regional lung trauma from mechanical ventilation, may be found in the patient with smoke inhalation. We now appreciate that energy transfer principles may affect optimal ventilator management and come into play in damaged heterogenous lungs. Mechanical ventilation in the patient with inhalation injury should consider various factors. Self-injurious respiratory demand by the patient can be reduced using analgesia and sedation. Dynamic factors beginning with rate management can reduce the incidence of potentially damaging ventilation. Moreover, preclinical study is underway to examine the flow of gas based on the ventilator mode selected, which may also be a factor triggering regional lung injury.

Locoregional therapies for hepatocellular carcinoma: which patients are most likely to gain a survival advantage?

BACKGROUND AND AIM: Locoregional therapies for hepatocellular carcinoma (HCC) are considered to confer a survival advantage, however, the patient group that should be targeted is not clearly defined. This study aimed to determine the impact on survival of locoregional therapies compared with supportive care, within prognostic categories as stratified by the Cancer of the Liver Italian Program (CLIP) scoring system. METHODS: A prospective database was used to identify those patients who were treated with either locoregional therapy (n = 128) or supportive care (n = 92). Survival analysis was performed for groups matched by CLIP score at presentation. Comparison of important prognostic factors was undertaken and univariate and multivariate analysis was performed to assess determinants of survival. RESULTS: Use of locoregional therapies was only associated with a survival benefit in patients with a CLIP score of 1 or 2. In this group, the median survival in patients who received locoregional therapies was 25.0 months (95% confidence interval 22.7-27.4) compared with 8.9 months (95% confidence interval 7.3-10.5) for supportive care (P = 0.001). For patients with CLIP scores of 3 or greater, no survival benefit of locoregional therapies was observed. Multivariate analysis revealed locoregional intervention, CLIP score, tumor symptoms, alpha-fetoprotein level, bilirubin and alkaline phosphatase level as independent prognostic indicators. CONCLUSION: Locoregional therapies should be targeted specifically to patients with non-advanced hepatocellular carcinoma as assessed by validated scoring systems. Use of these therapies in patients with advanced disease does not appear to be associated with a survival benefit and may expose patients to unnecessary harm.

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

UNLABELLED: Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. AIMS: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. METHOD: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. RESULTS: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). CONCLUSION: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.

Pharmacotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the more common causes of cancer death worldwide. It occurs on a background of chronic liver disease or viral hepatitis in the vast majority of cases, with hepatitis C being mostly responsible for its continuing rise in western countries. With the screening of at-risk groups, up to 70% of HCC lesions will be detected at a treatable stage but at best, only 20-30% will benefit from potentially curative hepatic resection or transplantation. How best to treat the remaining nonsurgical patients is an area of much debate and no ideal treatment is yet available. This review summarises some of the therapeutic modalities used for HCC, with an emphasis on pharmacological therapies.