Hepatocellular carcinoma: trends of incidence and survival in Europe and the United States at the end of the 20th century

OBJECTIVES: There is large geographic variation in incidence levels and time trends of hepatocellular carcinoma. We compared population-based liver cancer incidence and survival in European and U.S. populations in order to elucidate geographic differences and time trends for these variables. METHODS: Since comparisons based on cancer registry data are problematic because of variations in liver cancer definition and coding, we considered a subset of cases likely to be mainly hepatocellular carcinoma, suitable for international comparison. Incidence and 5-yr relative survival were calculated from cases diagnosed in five European regions (30,423 cases) and the United States (6,976 cases) in 1982-1994. RESULTS: Age-standardized incidence was highest in southern Europe (12/100,000 in men and 3/100,000 in women in 1992-94) and lowest in northern Europe, where incidence was similar to that of the United States (3/100,000 in men, <1/100,000 in women). Over the study period, incidence remained stable in the United States and most of Europe, except for a notable increase in southern Europe. Five-year relative survival was <10% in Europe, ranging from 8% (southern Europe) to 5% (eastern Europe), and 6% in the United States. Survival increased slightly with time, mainly in southern Europe and was unaffected by sex, but was better in younger patients. CONCLUSIONS: Increasing incidence in southern Europe is probably related to hepatitis B and C infection and increasing alcohol intake, while improving survival may be due to greater surveillance for cirrhosis. The survival gap between clinical and population-based series suggests management is better in centers of excellence.     

Development of a new PCR protocol to detect and subtype Blastocystis spp. from humans and animals

Blastocystis spp. is commonly found in the feces of humans worldwide. Infection has been reported as asymptomatic, acute symptomatic, and chronic symptomatic. This wide range of responses to infection could be related to the genetic diversity of morphologically indistinguishable specimens obtained from infected hosts. The former name Blastocystis hominis is now reported as Blastocystis spp. because of its genetic diversity. Blastocystis is recognized as a complex of subtypes that have not been fully characterized as independent species. The finding of Blastocystis spp. in feces from several animal species suggests a zoonotic potential. Based on conserved regions of published nucleotide SSU rDNA sequences from all Blastocystis subtypes found in GenBank, a PCR and sequencing protocol was developed. The ~500 bp SSU rDNA gene fragment amplified by this PCR is highly sensitive compared with published primers and contains highly variable regions that allow phylogenetic analysis of Blastocystis. These primers were used to detect and subtype Blastocystis spp. specimens from naturally infected humans, primates, cattle, pigs, and chickens. Based on these findings, application of this method can elucidate the complexity of this heterogeneous genus and its role in human and animal disease, as well as its zoonotic potential.     

Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance

Santón A, García‐Cosío M, Cristóbal E, Pascual A, Muriel A & García‐Laraña J (2011) Histopathology 58, 1072–1080 Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome. Methods and results: Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs [10, 27, 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stress‐response inhibitors. Active caspases 3, 8 and 9 were detected in 55.1%, 55.4% and 96.2% of cases although cleaved poly (ADP‐ribose) polymerase (PARP) was observed in only 16.1%, suggesting an improper functioning of apoptosis. Statistical analysis showed associations of HSP70 with active caspase 3 (P = 0.000); HSP40 with active caspase 9 (P = 0.031) and p53 (P = 0.003); HO1 with p53 (P = 0.006) and p21 (P = 0.005); and p53 with p21 (P = 0.015). Conclusions: Correlations between the expression of apoptotic markers and HSPs may suggest a role for the latter in modulating apoptosis in cHL, mainly through the HSP70‐HSP40 system, and in the stabilization of p53. Survival analyses showed that absence of active caspase 8 and HO1 had a negative impact in patient outcome.     

Short-course montelukast for intermittent asthma in children: a randomized controlled trial

RATIONALE: In children, intermittent asthma is the most common pattern and is responsible for the majority of exacerbations. Montelukast has a rapid onset of action and may be effective if used intermittently. OBJECTIVES: To determine whether a short course of montelukast in children with intermittent asthma would modify the severity of an asthma episode. METHODS: Children, aged 2-14 years with intermittent asthma participated in this multicenter, randomized, double-blind, placebo-controlled clinical trial over a 12-month period. Treatment with montelukast or placebo was initiated by parents at the onset of each upper respiratory tract infection or asthma symptoms and continued for a minimum of 7 days or until symptoms had resolved for 48 hours. MEASUREMENTS AND MAIN RESULTS: A total of 220 children were randomized, 107 to montelukast and 113 to placebo. There were 681 treated episodes (345 montelukast, 336 placebo) provided by 202 patients. The montelukast group had 163 unscheduled health care resource utilizations for asthma compared with 228 in the placebo group (odds ratio, 0.65; 95% confidence interval, 0.47-0.89). There was a nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and beta-agonist and prednisolone use. Symptoms were reduced by 14% and nights awakened by 8.6% (p = 0.043), and days off from school or childcare by 37% and parent time off from work by 33% (p < 0.0001 for both). CONCLUSIONS: A short course of montelukast, introduced at the first signs of an asthma episode, results in a modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work in children with intermittent asthma.     

Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study

Effective treatments for testicular cancer have been available since the 1970s, yet EUROCARE uncovered marked inter-country survival differences for this disease. To investigate these differences, we reviewed clinical records of 1350 testicular cancer cases diagnosed during 1987-1992 from 13 population-based cancer registries in nine European countries. Patients were followed up for life status and relapse. Ten-year observed survival was estimated by the Kaplan-Meier method. Cox multivariable analyses were performed separately for seminomas and non-seminomas. Overall, 66% of seminomas and 36% of non-seminomas were limited to the testis. Ten-year survival was 63% (Estonia) to 94% (Switzerland, Slovenia) for seminoma; 47% (Estonia) to 90% (Yorkshire, UK, The Netherlands) for non-seminoma. Multivariable analysis adjusted for country, age and stage showed that hazard ratios (HRs) of death differed little between western European registries, and were mainly attributable to differing stage at diagnosis. Significantly higher than reference HRs in Estonia and Poland suggest inadequacy or unavailability of treatments.     

The impact of DM on MHC class II-restricted antigen presentation can be altered by manipulation of MHC-peptide kinetic stability

DM edits the peptide repertoire presented by major histocompatibility complex class II molecules by professional antigen-presenting cells (APCs), favoring presentation of some peptides over others. Despite considerable research by many laboratories, there is still significant uncertainty regarding the biochemical attributes of class II-peptide complexes that govern their susceptibility to DM editing. Here, using APCs that either do or do not express DM and a set of unrelated antigens, we found that the intrinsic kinetic stability of class II-peptide complexes is tightly correlated with the effects of DM editing within APCs. Furthermore, through the use of kinetic stability variants of three independent peptides, we demonstrate that increasing or decreasing the kinetic stability of class II-peptide complexes causes a corresponding alteration in DM editing. Finally, we show that the spontaneous kinetic stability of class II complexes correlates directly with the efficiency of presentation by DM+ APCs and the immunodominance of that class II-peptide complex during an immune response. Collectively, these results suggest that the pattern of DM editing in APCs can be intentionally changed by modifying class II-peptide interactions, leading to the desired hierarchy of presentation on APCs, thereby promoting recruitment of CD4 T cells specific for the preferred peptides during an immune response.     

Out-of-pocket costs sustained in the last 12 months by cancer patients: an Italian survey-based study on individual expenses between 2017 and 2018

The European Journal of Health Economics - Out of Pocket costs (OOP) sustained by cancer patients also in public NHS contribute to disease-related financial toxicity. Aim of the study was to...