Background: The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied but data on survival are still equivocal. Objective: To assess the effectiveness of chemoradiotherapy followed by surgery in the reduction of mortality in patients with resectable oesophageal cancer. Methods: Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2002) were supplemented with hand searches of reference lists. Study selection: Studies were included if they were randomised controlled trials (RCTs) comparing preoperative chemoradiotherapy plus surgery with surgery alone, and if they included patients with resectable histologically proven oesophageal cancer without metastatic disease. Six eligible RCTs were identified and included in the meta-analysis. Data extraction: Data on study populations, interventions, and outcomes were extracted from each RCT according to the intention to treat method by three independent observers and combined using the DerSimonian and Laird method. Results: Chemoradiotherapy plus surgery compared with surgery alone significantly reduced the three year mortality rate (odds ratio (OR) 0.53 (95% confidence interval (CI) 0.31–0.93); p = 0.03) (number needed to treat = 10). Pathological examination showed that preoperative chemoradiotherapy downstaged the tumour (that is, less advanced stage at pathological examination at the time of surgery) compared with surgery alone (OR 0.43 (95% CI 0.26–0.72); p = 0.001). The risk for postoperative mortality was higher in the chemoradiotherapy plus surgery group (OR 2.10 (95% CI 1.18–3.73); p = 0.01). Conclusions: In patients with resectable oesophageal cancer, chemoradiotherapy plus surgery significantly reduces three year mortality compared with surgery alone. However, postoperative mortality was significantly increased by neoadjuvant chemoradiotherapy. Further large scale multicentre RCTs may prove useful to substantiate the benefit on overall survival.

Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and higher stages of fibrosis in patients with CHC resulting from genotype 1 HCV (G1-HCV). Two hundred one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Nondiabetic patients were defined as insulin resistant if HOMA-IR was >2.7. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis. Ninety-six patients were noninsulin resistant (group 1), 76 were insulin resistant without diabetes (group 2), and 29 were diabetic (group 3). At multivariate analysis, fibrosis of ≥3 was independently associated with high necroinflammatory activity (odds ratio [OR] 2.994, 95% confidence interval [CI] 1.422–6.098), low platelets (OR 0.994, 95% CI 0.981–0.999), low cholesterol (OR 0.987, 95% CI 0.976–0.998), high ferritin (OR 1.002, 95% CI 1.001–1.004), and a high prevalence of IR (OR 2.692, 95% CI 1.463–4.954). Diabetic patients were twice as likely to have severe fibrosis (60%) than those with IR but no diabetes (30%) (P = 0.006). The degree of steatosis and that of fibrosis were weakly associated with each other (P = 0.42). In subjects with CHC resulting from G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis, regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients ( P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis ( P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). Conclusion: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients. (Hepatology 2012)