Anaemia is independently associated with mortality in patients with hepatocellular carcinoma.

BACKGROUND: Anaemia is frequent in patients with cancer and/or liver cirrhosis and is associated with impaired quality of life. Here, we investigated the impact of anaemia on overall survival (OS) and clinical characteristics in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: HCC patients treated between 1992 and 2018 at the Medical University of Vienna were retrospectively analysed. Anaemia was defined as haemoglobin level <13 g/dl in men and <12 g/dl in women. RESULTS: Of 1262 assessable patients, 555 (44.0%) had anaemia. The main aetiologies of HCC were alcohol-related liver disease (n = 502; 39.8%) and chronic hepatitis C (n = 375; 29.7%). Anaemia was significantly associated with impaired liver function, portal hypertension, more advanced Barcelona Clinic Liver Cancer stage and elevated C-reactive protein (CRP). In univariable analysis, anaemia was significantly associated with shorter median OS [9.5 months, 95% confidence interval (95% CI) 7.3-11.6 months] versus patients without anaemia (21.5 months, 95% CI 18.3-24.7 months) (P < 0.001). In multivariable analysis adjusted for age, Model for End-stage Liver Disease, number of tumour nodules, size of the largest nodule, macrovascular invasion, extrahepatic spread, first treatment line, alpha-fetoprotein and CRP, anaemia remained an independent predictor of mortality (adjusted hazard ratio 1.23, 95% CI 1.06-1.43, P = 0.006). CONCLUSIONS: Anaemia was significantly associated with mortality in HCC patients, independent of established liver- and tumour-related prognostic factors. Whether adequate management of anaemia can improve outcome of HCC patients needs further evaluation.

Diallyl sulfide enhances azoxymethane-induced preneoplasia in Fischer 344 rat colon.

Azoxymethane (AOM) is an indirect-acting colon carcinogen that produces a high incidence of precancerous lesions, referred to as aberrant crypt foci (ACF), in rats. This study was undertaken to determine whether high dose gavage administration of the cytochrome P-450 2E1 (CYP2E1) inhibitor and chemopreventive agent, diallyl sulfide, would reduce the incidence and severity of ACF formation in the distal colons of AOM-treated Fischer 344 rats. Seven-week-old male rats received 150 or 50 mg/kg diallyl sulfide by gavage 24 and 2 h prior to two weekly i.p. injections of AOM (20 mg/kg). Ten weeks after the last injection of AOM the rats were sacrificed and the colons removed and stained with 0.2% methylene blue. ACF were visualized using stereomicroscopy. Rats pretreated with diallyl sulfide exhibited a significant increase in the number of ACF/cm in the distal colon compared with rats receiving AOM alone. This increase in ACF number was seen in ACF of all sizes. To examine the effects of diallyl sulfide on the initiation stage of AOM-induced carcinogenesis, mutations in the K-ras proto-oncogene were also investigated. ACF and normal appearing colonic mucosa (0.2-0.5 mm3) were microdissected for subsequent PCR-RFLP analysis of a codon 12 (GGT-GGA) activating mutation in the K-ras gene. Greater than 90% of ACF from AOM-treated animals, regardless of diallyl sulfide treatment, exhibited activating K-ras mutations. K-ras mutations were also detected in normal appearing mucosa of AOM-treated animals, although at a lesser frequency (15-35%). These studies demonstrate that diallyl sulfide given in large gavage doses enhances AOM-induced preneoplasia in rats and suggests that diallyl sulfide may alter the disposition of AOM intermediates and/or enhance colonic promotional activity in the rat.