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[Management of malignant bowel obstruction in terminal care--is home care possible?].

Malignant bowel obstruction occurs in about 10% of those with advanced abdominal cancer and in about 25% of those with advanced pelvic cancer. Such patients usually develop nausea, vomiting, constipation, abdominal dilatation and colicky pain. Traditional therapy consists of intravenous fluids and decompression by duodenal tube, gastrostomy or operation but postoperative mortality is high. Treatment requires hospitalization and therefore such patients have not been considered candidates for home care. Palliative medical techniques can cope with this syndrome and allow home care. Hypodermoclysis, non-prokinetic antiemetics like haloperidol and scopolamine, octeotride, corticosteroids, and narcotics for severe abdominal pain can alleviate symptoms. Medications can be combined and infused subcutaneously in a syringe driver and patients can remain with their families in their natural environment. Such techniques can give these patients who have short life expectancies reasonable quality of life.

Abdominal Neoplasms↗

Efficacy of EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer with EGFR exon 19 insertions: clinical-genomic, preclinical analysis through LC-SCRUM-Asia (multi-institutional genomic screening registry).

BACKGROUND: EGFR exon 19 insertions (EGFRex19ins) are rare EGFR mutations. Their clinical-genomic characteristics and outcomes with EGFR-tyrosine kinase inhibitors (TKIs) remain uncertain. METHODS: We evaluated the clinical-genomic characteristics and outcomes of EGFR-TKIs for EGFRex19ins in the multi-institutional prospective lung cancer genomic screening project (LC-SCRUM-Asia). We also studied preclinical Ba/F3 models expressing EGFR-K745_E746insIPVAIK (Ba/F3-IPVAIK) to investigate their sensitivity to 1st-, 2nd-, 3rd-generation, and EGFR exon 20 insertion-active TKIs. RESULTS: In LC-SCRUM-Asia, 16,204 NSCLC patients were enrolled from March 2015 to December 2023. EGFRex19ins were detected in 13 samples (0.1 % of NSCLC). The median age was 72 years (range, 38-80); most patients were female (77 %), had adenocarcinoma (92 %), and were never-smokers (62 %). Twelve patients (93 %) had EGFR-K745_E746insIPVAIK, while one (7 %) had EGFR-K745_E746insVPVAIK. The most frequent co-mutation was TP53 (62 %); no patients had other driver alterations. Six patients (46 %) tested positive for EGFR exon 19 deletions with PCR-based Cobas EGFR test, likely due to cross-reactivity arising from sequence homology. Twelve patients received EGFR-TKIs; five (42 %) experienced partial response. In the preclinical study, Ba/F3-IPVAIK showed the highest sensitivity to 2nd-generation EGFR-TKIs compared to other EGFR-TKIs. Structural studies supported these consistent results. When broken down by EGFR-TKI generations, response rates for 1st-, 2nd-, and 3rd-generation TKIs were 50 % (1/2), 80 % (4/5), and 0 % (0/5), respectively. The median PFS for 1st-, 2nd-, and 3rd-generation TKIs were 8.7 (95 % CI, 7.4-NR), 14.7 (95 % CI, 8.0-NR), and 4.4 (95 % CI, 3.4-NR) months, respectively. CONCLUSION: Our preclinical, structural, and clinical findings indicate 2nd-generation EGFR-TKIs are more effective for EGFRex19ins compared to other TKIs.

Adult↗

Comparative genomic analysis of key oncogenic pathways in hepatocellular carcinoma among diverse populations.

BACKGROUND/OBJECTIVES: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with significant racial and ethnic disparities in incidence, tumor biology, and clinical outcomes. Hispanic/Latino (H/L) patients tend to be diagnosed at younger ages and more advanced stages than Non-Hispanic White (NHW) patients, yet the molecular mechanisms underlying these disparities remain poorly understood. Key oncogenic pathways, including RTK/RAS, TGF-Beta, WNT, PI3K, and TP53, play pivotal roles in tumor progression, treatment resistance, and response to targeted therapies. However, ethnicity-specific alterations within these pathways remain largely unexplored. This study aims to compare pathway-specific mutations in HCC between H/L and NHW patients, assess tumor mutation burden, and identify ethnicity-associated oncogenic drivers using publicly available datasets. Findings from this analysis may inform precision medicine strategies for improving early detection and targeted therapies in underrepresented populations. METHODS: We conducted a bioinformatics analysis using publicly available HCC datasets to assess mutation frequencies in RTK/RAS, TGF-Beta, WNT, PI3K, and TP53 pathway genes. The study included 547 patients, consisting of 69 H/L patients and 478 NHW patients. Patients were stratified by ethnicity (H/L vs. NHW) to evaluate differences in mutation prevalence. Chi-squared tests were used to compare mutation frequencies, while Kaplan-Meier survival analysis assessed overall survival differences associated with pathway-specific alterations in both populations. RESULTS: Significant differences were observed in the RTK/RAS pathway related genes, particularly in FGFR4 mutations, which were more prevalent in H/L patients compared to NHW patients (4.3% vs. 0.6%, p = 0.02). Additionally, IGF1R mutations exhibited borderline significance (7.2% vs. 2.9%, p = 0.07). In the PI3K pathway, INPP4B alterations were more frequent in H/L patients than in NHW patients (4.3% vs. 1%, p = 0.06), while in the TGF-Beta pathway, TGFBR2 mutations were more common in H/L patients (2.9% vs. 0.4%, p = 0.07), suggesting potential ethnicity-specific variations. Survival analysis revealed no significant differences in overall survival between H/L and NHW patients, indicating that molecular alterations alone may not fully explain survival disparities and suggesting a role for additional factors such as immune response, environmental exposures, or access to targeted therapies. CONCLUSIONS: This study provides one of the first ethnicity-focused analyses of key oncogenic pathway alterations in HCC, revealing distinct molecular differences between H/L and NHW patients. The findings suggest that RTK/RAS (FGFR4, IGF1R), PI3K (INPP4B), and TGF-Beta (TGFBR2) pathway alterations may play a distinct role in HCC among H/L patients, while their prognostic significance in NHW patients remains unclear. These insights emphasize the importance of incorporating ethnicity-specific molecular profiling into precision medicine approaches to improve early detection, targeted therapies, and clinical outcomes in HCC, particularly for underrepresented populations.

PI3K pathway↗

A comparison of hospital-based charges following partial and radical nephrectomy.

OBJECTIVE: Recent studies demonstrate similar survival rates in patients treated with either partial or radical nephrectomy for renal tumors less than 4 cm. We retrospectively compared the hospital based charges for these two procedures in a similar cohort of patients treated at Memorial Sloan-Kettering Cancer Center. PATIENTS AND METHODS: A retrospective review of 103 consecutive cases of renal tumors less than 4 cm treated by either radical or partial nephrectomy from 1996 to 1999 was conducted. Overall hospital charges were calculated by analyzing 18 separate departmental charge categories including room and board, pharmacy, radiologic tests, operating room charges, and laboratory services. RESULTS: A total of 66 partial and 37 radical nephrectomies were analyzed. No difference was found in the mean charge per procedure ($16,660, partial and $16,545, radical); (p > .05). The major cost drivers for partial and radical nephrectomy respectively were: 1) room and board, 42% and 44%; 2) operating room charges, 28% and 25%; 3) pathology, 6% and 6%; 4) recovery room, 6% and 7%; and 5) biochemistry, 5% and 5%. Significant increases in charges for partial nephrectomy were noted from the blood bank services and intraoperative surgical supplies. The median length of stay (5 days) was identical for partial and radical nephrectomy. No difference was found in the complication rate for these procedures (p > .05). CONCLUSION: Hospital-based charges for radical and partial nephrectomy are similar at when performed at a tertiary care referral center.

Adult↗

Depression: cost-of-illness studies in the international literature, a review.

BACKGROUND: Depression is one of the most ancient and common diseases of the human race and its burden on society is really impressive. This stems both from the epidemiological spread (lifetime prevalence rate, up to 30 years of age, was estimated as greater than 14.4% by Angst et al.) and from the economic burden on healthcare systems and society, but also as it pertains to patient well-being. AIMS OF THE STUDY: The scope of this review was to examine studies published in the international literature to describe and compare the social costs of depression in various countries. METHODS: A bibliographic search was performed on international medical literature databases (Medline, Embase), where all studies published after 1970 were selected. Studies were carefully evaluated and only those that provided cost data were included in the comparative analysis; this latter phase was conducted using a newly developed evaluation chart. RESULTS: 10 abstracts were firstly selected; 46 of them underwent a subsequent full paper reading, thus providing seven papers, which were the subject of the in-depth comparative analysis: three studies investigated the cost of depression in the USA, three studies in the UK and one study was related to Italy. All the studies examined highlight the relevant economic burden of depression; in 1990, including both direct and indirect costs, it accounted for US$ 43.7 billion in the US (US$ 65 billion, at 1998 prices) according to Greenberg and colleagues, whilst direct costs accounted for £417 million in the UK (or US$ 962.5 million, at 1998 prices), according to Kind and Sorensen. Within direct costs, the major cost driver was indeed hospitalization, which represented something in between 43 and 75% of the average per patient cost; conversely, drug cost accounted for only 2% to 11% in five out of seven studies. DISCUSSION: Indeed, our review suggests that at the direct cost level, in both the United States and the United Kingdom, the burden of depression is remarkable, and this is confirmed by a recent report issued by the Pharmaceutical Research and Manufacturers Association (PhRMA) where prevalence and cost of disease were compared for several major chronic diseases, including Alzheimer, asthma, cancer, depression, osteoporosis, hypertension, schizophrenia and others: in this comparison, depression is one of the most significant diseases, ranked third by prevalence and sixth in terms of economic burden. Moreover, in terms of the average cost per patient, depression imposes a societal burden that is larger than other chronic conditions such as hypertension, rheumatoid arthritis, asthma and osteoporosis. The application of economic methods to the epidemiological and clinical field is a relatively recent development, as evidenced by the finding that, out of the seven studies examined, three refer to the US environment, three to the UK and one to Italy, while nothing was available about the cost of depression for large countries such as France, Germany, Spain, Japan and others. IMPLICATION FOR HEALTH CARE PROVISION AND USE: The high incidence of hospitalization, and the finding that drug cost represents only a minor component of the total direct cost of the disease, suggests that room is still available for disease management strategies that, while effectively managing the patient's clinical profile, could also improve health economic efficiency. IMPLICATION FOR HEALTH POLICIES: Disease management strategies, with particular emphasis on education, should be targeted not only at patients and medical professionals but also at health decision makers in order "to encourage effective prevention and treatment of depressive illness". IMPLICATIONS FOR FURTHER RESEARCH: Cost of illness studies are a very useful tool allowing cost data comparisons across countries and diseases: for this reason, we suggest that further research is needed especially in some western European countries to assess the true economic burden of depression on societies.

Journal Article↗

Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.

PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma. EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles with a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBL) that were reliably detectable in cell-free DNA (cfDNA). Marker robustness and specificity were validated using independent neuroblastoma methylation datasets and assessed against methylation profiles from other cancer types. We established neuroblastoma as a distinct methylation entity within the reference atlas by integrating a panel of 25 meNBLs, enabling quantitative estimation of tumor-derived cfDNA. Assay performance was evaluated across diagnostic, remission, relapse, and healthy control samples and compared with mutation-based and copy number-based approaches. RESULTS: Neuroblastoma-derived cfDNA was consistently detected at diagnosis and relapse but was absent in healthy controls and during confirmed remission. Methylation-based deconvolution demonstrated high specificity, with no detectable background signal in controls, and improved performance relative to copy number-based tumor fraction estimation. Longitudinal profiling enabled early molecular detection of relapse and reliable disease monitoring. CONCLUSIONS: We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients, including those lacking trackable genomic alterations. This approach supports the clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

Humans↗

A gene-environment interaction between occupation and BRCA1/BRCA2 mutations in male breast cancer?

The association of male breast cancer (MBC) with a positive breast cancer (BC) family history and with BRCA1/2 germ-line mutations points to a genetic component; a relationship with occupation has also been reported. Recently, we identified pathogenetic BRCA1/2 mutations in a population-based series of Italian MBC patients: here in, we investigated interactions between a carrier status for BRCA1/2 mutations and occupation using a case-case design and estimating case-only odds ratios (CORs). Truck-driving was the most frequent occupation (3/4 BRCA-related cases and 2/19 unrelated cases). An interaction between carrier status and working as a truck-driver emerged, when we classified MBC cases as "ever/never-held" this job title (COR 25.5; 95% Confidence Limits (CL): 1.1-1,412.5) or according to truck-driving as the "longest-held" work (COR 54.0; 95% CL: 1.6-2,997.5). The possible modifying effect on MBC risk in subjects carrying BRCA1/2 germ-line mutations of an occupation characterised by exposure to chemicals such as polycyclic aromatic hydrocarbons (PAH) that are capable of inducing DNA damage, may provide clues to the role of environmental exposures in modifying BC risk in mutation carriers in both genders.

Adult↗

High affinity DNA-microtubule interactions: evidence for a conserved DNA-MAP interaction involving unusual high CsCl density repetitious DNA families.

We have examined high affinity interactions of chick brain microtubule proteins with 35S labelled tracer DNAs from chick, mouse and D. melanogaster under equilibrium conditions by the nitrocellulose filter binding technique. Ternary reaction mixtures of the above two components and a third component, an excess of unlabelled competitor DNA from either E. coli., mouse, D. melanogaster or chick, were used to measure small fractions of DNA in each case (1-4%) bound to microtubule protein under high stringency- large competitor DNA concentration and 0.5 M NaCl. As seen in part previously (Marx, K.A. and Denial, T. (1985) in The Molecular Basis of Cancer, 172B, 65-75 (Rein, ed), A. Liss, N.Y.) the measured order of competitor DNA strengths was identical for all three tracer DNAs. That is: chick > mouse > D. melanogaster > E. coli competitor DNA. Since the homologous interaction, chick competitor DNA with chick brain microtubule protein, is always the strongest interaction measured, we interpret this as evidence for a conserved protein-DNA sequence interaction. 35S chick DNA tracer sequences, isolated from nitrocellulose filters following the stringent binding in the presence of 0.9 mM-1 E. coli. competitor DNA, was used in driven reassociation reactions with total chick driver DNA. This fraction was found to be significantly enriched in repetitive chick DNA sequences. Since we have observed a similar phenomenon in mouse, we then compared the stringent binding mouse sequences and showed that the bulk of these sequences did not cross-hybridize with total chick DNA. Finally, all three 35S tracer DNAs binding to nitrocellulose were isolated and sedimented to equilibrium on CsCl density gradients. The CsCl density distributions from all three DNAs showed significant (100-fold) enrichment in classical satellite DNAs as well as higher enrichment in two very unusual high CsCl density families of DNA (1.720-1.740 g/cm3; 1.750-1.765 g/cm3). These families are never observed as distinct bands in total DNA CsCl gradients, nor could we isolate them in purified tubulin control binding experiments. This apparently general phenomena may be identifying some of the sequence families involved in the high affinity microtubule interaction, which appears to be conserved in evolution.

Animals↗

Cloning differentially expressed genes by linker capture subtraction.

We have developed a simple and effective method, designated linker capture subtraction (LCS), for cloning differentially expressed genes between two cell types or between cells treated in two different ways. In the first step of the method, two mRNA populations are converted to double-stranded cDNAs, fragmented, and ligated to linkers for PCR amplification. In the second step, the linkered DNA (tester) from one mRNA population is hybridized to an excess of the unlinkered DNA (driver) from the other mRNA population, followed by incubation with mung bean nuclease which digests single-stranded DNA specifically. This leaves only tester-tester homohybrids to be amplified by PCR in the following step, so as to achieve an enrichment of tester-specific sequences. The amplified PCR products are then used as tester for another round of subtraction. The process of subtraction is carried out three times, and the final PCR products are inserted into a vector for clonal analysis. We have used the strategy to begin to clone and identify the genes expressed differentially between the human prostate cancer cell lines LNCaP and PC-3, which have different tumorigenic and metastatic potentials. We demonstrated strong enrichment of target sequences. We also report the identities of two of the genes expressed differentially in these cell lines. One is prostate-specific antigen (PSA) which is known to be expressed in LNCaP but not in PC-3. The other is vimentin, the differential expression of which has not been reported previously in these prostate cancer cells.

Base Sequence↗

[Hospice care and the treatment of cancer pain].

The history of hospice care in Great Britain was first introduced, and the pioneer work carried out by the founder of the modern hospice care, Dame Cicely Saunders was briefly described. The first duty of the hospice to patients with terminal cancer is to eliminate physical pain, especially intractable severe pain, which may deteriorate the quality of the patient's life. For this purpose, morphine and its derivatives should be the panacea of choice, although it is of importance to initially determine the appropriate, i.e. completely analgesic level combined with euphoria and anxiolysis, then to maintain this level continuously without somnolence or other dysphoric effects. The dose differs quite markedly according to each patient and the severity of pain. To maintain the level of analgesia, the oral use of morphine at four-hour internals is required, or continuous hypodermic administration by means of a syringe driver is quite ideal. In Japan, the use of diamorphine (heroin) is strictly forbidden, and therefore, a non-narcotic and potent analgesic morphine antagonists, e.g. buprenorphine (Lepetan) has been used by continuous hypodermic administration with a syringe driver by Umeda et al. of Kyoto University Hospital, at a dose of 4-8 micrograms/kg of body weight/day with favorable results. Hospice care should now be considered to be a new concept of medical treatment or a new medical field which must include not only the patient himself with incurable malignant disease but also his family or relatives in considering the target of treatment and care, in order to improve the quality of the patient's life even though shortened by the malignancy.

Analgesics↗

Molecular epidemiology studies of carcinogenic environmental pollutants. Effects of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on exogenous and oxidative DNA damage.

Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment. The application of such techniques has been mostly concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) that are associated with particulate matter in air pollution, and has showed clear evidence of genotoxic effects, such as DNA adducts, chromosome aberrations (CA) and ras oncogene overexpression, in environmentally exposed Czech and Polish populations. We are currently extending these studies by an investigation of populations exposed to environmental pollution in three European countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular attention to PAHs, but also investigates the extent of radically induced (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and controls, who carried personal monitors to determine their exposures to PAHs have been studied, and blood and urine were collected. Antioxidant and dietary status were assessed in these populations. Stationary monitors were also used for ambient air monitoring. Amongst the parameters studied in the biological samples were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1) protein levels, (b) oxidative DNA damage, (c) the biological effect of the exposure by measurement of chromosome damage by fluorescence in situ hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen metabolising and DNA repair enzymes. Repair ability was also measured by the Comet assay. In vitro systems are being evaluated to characterise the genotoxicity of the organic compounds adsorbed to air particles.

Biomarkers↗

Differential gene expression in patients genetically predisposed to pancreatic cancer.

BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. RESULTS: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

Adenocarcinoma↗

Wood-related occupations and laryngeal cancer.

A case-control study was carried out among male residents in Madrid from 1982 through 1985 to ascertain occupational risk for laryngeal cancer. The study covered 50 histologically confirmed cases, 43 hospital, and 46 population controls. Occupational history and lifetime consumption patterns for cigarettes and alcohol were obtained by interview. Risk estimates, adjusted for tobacco and alcohol consumption, were calculated using nonconditional logistic regression. The highest odds ratio (OR) corresponded to woodworkers. For them, the risk increased with duration of exposure and decreased with the number of years elapsed since leaving it. The OR for woodworkers exposed over 20 years was 5.63, 95% confidence interval (CI) 1.15 to 26.64, being even greater in the furniture workers subgroup, OR 6.67 (95% CI 1.05 to 42.57). Other occupational categories with high OR were transport drivers (OR 3.31, 95% CI 0.98 to 11.22) and bricklayers and masons (OR 2.31, 95% CI 0.85 to 6.33). Wood dust or chemical compounds used in the treatment of the wood could underlie the strongest association found.

Aged↗

The influence of UV radiation on protistan evolution.

Ultraviolet radiation has provided an evolutionary challenge to life on Earth. Recent increases in surficial ultraviolet B fluxes have focused attention on the role of UV radiation in protistan ecology, cancer, and DNA damage. Exploiting this new wealth of data, I examine the possibility that ultraviolet radiation may have played a significant role in the evolution of the first eukaryotes, that is, protists. Protists probably arose well before the formation of a significant ozone shield, and thus were probably subjected to substantial ultraviolet A, ultraviolet B, and ultraviolet C fluxes early in their evolution. Evolution consists of the generation of heritable variations and the subsequent selection of these variants. Ultraviolet radiation has played a role both as a mutagen and as a selective agent. In its role as a mutagen, it may have been crucial in the origin of sex and as a driver of molecular evolution. As a selective agent, its influence has been broad. Discussed in this paper are the influence of ultraviolet radiation on biogeography, photosynthesis, and desiccation resistance.

Animals↗

From Antigenic Drive to Clonal Autonomy: An Update on Molecular Mechanisms of HCV-Related B-Cell Lymphomagenesis.

Chronic hepatitis C virus (HCV) infection is an established risk factor for B-cell lymphoproliferative disorders and represents a paradigmatic model of infection-driven lymphomagenesis. Although direct-acting antivirals have markedly reduced the burden of HCV-related disease, HCV-associated lymphomas continue to occur. Moreover, HCV screening remains incomplete in some geographical areas and healthcare settings, leaving a substantial proportion of infected individuals unaware of their status. This narrative review integrates current evidence on the mechanisms linking chronic HCV infection to mixed cryoglobulinemia and overt B-cell non-Hodgkin lymphoma. HCV lymphotropism and persistent antigenic stimulation could initially promote the selection and expansion of autoreactive B-cell clones, while mixed cryoglobulinemia represents the most informative pre-lymphomatous risk condition. Cytokine-mediated survival signals, particularly those involving B-cell activating factor, reinforce clonal persistence and cooperate with host genetic susceptibility, impaired apoptotic control, and activation-induced cytidine deaminase-mediated genomic instability. The progressive acquisition of somatic driver mutations, copy-number alterations, and epigenetic and transcriptomic changes may enable selected clones to escape functional anergy and become increasingly independent of the original viral stimulus that, in turn, represents an initial trigger of the lymphoproliferative process. Recurrent abnormalities converge on NF-κB, NOTCH, chromatin-regulatory, apoptotic, and cell-cycle pathways, although HCV-associated lymphomas remain molecularly heterogeneous. Emerging microRNA profiles further contribute to the molecular characterization of the transition from chronic infection and cryoglobulinemia to lymphoma. Despite the availability of highly effective antiviral therapies, HCV-associated lymphomagenesis remains clinically relevant and continues to provide an especially informative model for understanding how chronic viral infection can drive human cancer development.

B-cell lymphoproliferative disorders↗

Youth risk behavior surveillance--United States, 2003.

PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the leading causes of morbidity and mortality among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. REPORTING PERIOD: This report covers data collected during February-December 2003. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults--behaviors that contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity--plus overweight. YRBSS includes a national school-based survey conducted by CDC as well as state and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 32 state surveys, and 18 local surveys conducted among students in grades 9-12 during February-December 2003. RESULTS AND INTERPRETATION: In the United States, 70.8% of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2003 national Youth Risk Behavior Survey demonstrated that, during the 30 days preceding the survey, numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 30.2% had ridden with a driver who had been drinking alcohol; 17.1% had carried a weapon; 44.9% had drunk alcohol; and 22.4% had used marijuana. In addition, during the 12 months preceding the survey, 33.0% of high school students had been in a physical fight, and 8.5% had attempted suicide. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2003, 46.7% of high school students had ever had sexual intercourse; 37% of sexually active students had not used a condom at last sexual intercourse; and 3.2% had ever injected an illegal drug. Among adults aged > or =25 years, 62.9% of all deaths results from two causes: cardiovascular diseases and cancer. Results from the 2003 national Youth Risk Behavior Survey demonstrate that the majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2003, a total of 21.9% of high school students had smoked cigarettes during the 30 days preceding the survey; 78% had not eaten > or =5 servings/day of fruits and vegetables during the 7 days preceding the survey; 33.4% had participated in an insufficient amount of physical activity; and 13.5% were overweight. ACTIONS TAKEN: YRBSS data are being used to measure progress toward achieving 15 national health objectives for 2010 and three of the 10 leading health indicators. In addition, education and health officials at national, state, and local levels are using these YRBSS data to improve policies and programs to reduce priority health-risk behaviors among youth.

Adolescent↗

Alcohol and human cancer (review).

Epidemiological studies provide good evidence that alcoholic beverages are carcinogenic to the human liver, oesophagus, nasopharynx and larynx. There is some evidence that alcohol, when ingested in the form of beer, may be carcinogenic for the colon and rectum. Tenuous evidence exists for a link between cancer of the lung, urinary bladder, stomach and pancreas and alcohol consumption. The mechanism of action of alcohol as a carcinogen is not understood and it is likely that different mechanisms operate at different sites. Experimental models of alcohol carcinogenicity are largely unsatisfactory. However, it has been shown that alcohol can profoundly alter the metabolism of nitrosamines, which are known potent carcinogens, and may also act as a tumour promoter following initiation by nitrosamine.

Alcoholic Beverages↗

Youth risk behavior surveillance--United States, 1993.

PROBLEM/CONDITION: Priority health risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. REPORTING PERIOD: February through May 1993. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. The YRBSS includes a national, school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 24 state surveys, and nine local surveys conducted among high school students during February through May 1993. RESULTS AND INTERPRETATION: In the United States, 72% of all deaths among school-age youth and young adults are from four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1993 YRBSS suggest that many high school students practice behaviors that may increase their likelihood of death from these four causes: 19.1% rarely or never used a safety belt, 35.3% had ridden with a driver who had been drinking alcohol during the 30 days preceding the survey, 22.1% had carried a weapon during the 30 days preceding the survey, 80.9% ever drank alcohol, 32.8% ever used marijuana, and 8.6% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among adolescents also result from unintended pregnancies and sexually transmitted diseases, including human immunodeficiency virus (HIV) infection. YRBSS results indicate that in 1993, 53.0% of high school students had had sexual intercourse, 52.8% of sexually active students had used a condom during last sexual intercourse, and 1.4% ever injected an illegal drug. Among adults, 67% of all deaths are from three causes: heart disease, cancer, and stroke. In 1993, many high school students practiced behaviors that may increase the risk for these health problems: 30.5% of high school students had smoked cigarettes during the 30 days preceding the survey, only 15.4% had eaten five or more servings of fruits and vegetables during the day preceding the survey, and only 34.3% had attended physical education class daily. ACTIONS TAKEN: YRBSS data are being used nationwide by health and education officials to improve school health policies and programs designed to reduce risks associated with the leading causes of mortality and morbidity. At the national level, YRBSS data are being used to measure progress toward achieving 26 national health objectives and one of eight National Education Goals.

Accidents↗