Elevated prevalence of nodal positivity in carcinoid tumours of the appendix smaller than 2 cm has a negative impact on overall survival.

AIM: The current standard of care for clinically node-negative carcinoid tumours of the appendix < 2.0 cm in size is appendectomy alone. The aim of this analysis was to evaluate the prevalence of pathological nodal positivity in clinically node-negative appendiceal tumour specimens < 2.0 cm and quantify the impact of occult pathological nodal positivity on overall survival following resection. METHOD: A retrospective database review of the 2019 US National Cancer Database for appendiceal cancer identified 2007 cases of clinically node-negative appendiceal carcinoid tumours based on SEER histology codes 8240, 8241, 8242, 8243, 8243, 8244, 8245, 8246 and 8249. Kaplan-Meier with log-rank testing and multivariate Cox regression analysis evaluated the impact of occult nodal positivity on overall survival following resection for clinically node-negative appendiceal carcinoma. RESULTS: The prevalence of occult nodal positivity increased from 1.9% for sub-centimetre tumours to 7% for tumours between 1.0 and 1.5 cm, 16.5% for tumours between 1.5 and 2.0 cm and to >29.5% for tumours > 2.0 cm. Rates of metastatic spread were similar for tumours < 2.0 cm but increased for larger tumours. Over two-thirds of patients received a segmental colectomy as definitive surgical therapy. After controlling for differences in cohorts, multivariate analysis showed an increased hazard ratio for mortality of 162% (HR 2.62, CI 1.884-3.541) for patients with pathological node-positive disease. CONCLUSION: Clinically node-negative carcinoid tumours of the appendix bigger than 1.5 cm have an increased rate of occult nodal spread which has a negative impact on overall survival.

The influence of a novel edge enhancement software on image quality of DR hand images of patients with rheumatoid arthritis.

INTRODUCTION: This study aimed to evaluate the effects of a newly developed Advanced Edge Enhancement software (AEE) (Canon Europe, Amsterdam, NL) on image quality (IQ) of Digital Radiography (DR) hand images focusing on rheumatoid arthritis (RA). METHODS AND MATERIALS: Fifty posterior-anterior hand images with or suspected for RA were collected. For each of the 50 images, six copies were made with each their AEE algorithm settings. A total of 330 images (30 images iterated) were evaluated using relative Visual Grading Analysis (VGA) by three observers and combined into a VGA Score (VGAS). Second, 50 images of a technical Contrast Detail Radiography Phantom (CDRAD) was produced with three different AEE software settings, each at level 1,5 and without the AEE software yielding 350 CDRAD images. All images was analysed by the CDRAD Analyser and included for an objective analysis of the AEE software. RESULTS: The VGA study showed a significant difference in image quality between a standard image and images with AEE software applied. The average VGA score of the AEE software was better than the standard images (interval between 0.2 and 0.9). The AEE algorithms at level 5 scored significantly lower for noise but significantly higher for spatial resolution, sharpness and contrast in the VGA. The CDRAD images showed that all AEE algorithms had a statistically significant improvement for level 1 and deterioration for level 5 compared to the standard image. CONCLUSION: Overall the AEE algorithm: small structure level 1 showed an improvement of all IQ criteria in the VGA and a better technical IQ. IMPLICATIONS FOR PRACTICE: The AEE software ought to be considered as a useful addition to the current software, possibly enabling visualisation of structures currently visible.

Systemic IFN-beta gene therapy results in long-term survival in mice with established colorectal liver metastases.

Most patients succumbing to colorectal cancer fail with liver-predominant metastases. To make a clinical impact in this disease, a systemic or whole-liver therapy may be required, whereas most cancer gene therapy approaches are limited in their ability to treat beyond local disease. As a preclinical model for cancer gene therapy, recombinant adenovirus containing the human IFN-beta (hIFN-beta) cDNA was delivered systemically in nude mouse xenograft models of human colorectal cancer liver metastases. The vector targeted hepatocytes that produced high levels of hIFN-beta in the liver, resulting in a profound apoptotic response in the tumors and significant tumor regression. hIFN-beta gene therapy not only resulted in improved survival and long-term cure in a micrometastatic model, but provided similar benefits in a clinically relevant gross disease model. A similar recombinant adenovirus containing the murine IFN-beta (mIFN-beta) cDNA also resulted in a therapeutic response and improved survival in syngeneic mouse models of colorectal cancer liver metastases. Depletion studies demonstrate a contribution of natural killer cells to this therapeutic response. The toxicity of an adenoviral vector expressing murine IFN-beta in a syngeneic model is also presented. These encouraging results warrant further investigation of the use of cancer gene therapy for targeting metastatic disease.

Current perspectives on statins.

Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.

Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.

PURPOSE: To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS: Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS: Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION: Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.

The epidemiology of low levels of high-density lipoprotein cholesterol in patients with and without coronary artery disease.

Low levels of high-density lipoprotein cholesterol (HDL-C), and elevated total cholesterol-to-HDL-C ratios are independently associated with increased risk of coronary artery disease. In observational studies, every 1-mg/dL increment in HDL-C is associated with a 2% decreased risk of coronary artery disease in men and 3% decreased risk in women. On average, HDL-C levels are lower in men than in women, and are lower in whites than in blacks. Low HDL-C has also been found to be linked to higher risk of ischemic stroke, degree of carotid atherosclerosis, increased atherosclerotic progression as measured by coronary arteriography, higher coronary mortality among people with cardiovascular disease, and the development of coronary artery disease among patients with diabetes mellitus.

Revised methods for the Salmonella mutagenicity test.

The methods for detecting carcinogens and mutagens with the Salmonella mutagenicity test were described previously (Ames et al., 1975b). The present paper is a revision of the methods. Two new tester strains, a frameshift strain (TA97) and a strain carrying an ochre mutation on a multicopy plasmid (TA102), are added to the standard tester set. TA97 replaces TA1537. TA1535 and TA1538 are removed from the recommended set but can be retained at the option of the investigator. TA98 and TA100 are retained. We discuss other special purpose strains and present some minor changes in procedure, principally in the growth, storage, and preservation of the tester strains. Two substitutions are made in diagnostic mutagens to eliminate MNNG and 9-aminoacridine. Some test modifications are discussed.

Gene therapy of metastatic disease: progress and prospects.

Gene therapy remains a new and exciting therapy that holds the potential to impact the care of many diseases. Cancer gene therapy strategies encompass a major part of this developing field. Initial preclinical and phase I clinical trials have demonstrated the ability to transfer genetic material to cells in vitro and in vivo with resultant expression of biologically active protein. Most of these studies have involved direct injection or local installation of vector. A majority of patients succumbing to cancer do so because of metastatic disease. Clearly, to broaden the impact of cancer gene therapy on these patients' outcome, new strategies for targeting regional or systemic disease are required. This article offers a review of current vectors and therapeutic strategies along with the application of these in human cancers.

Nonlipid primary and secondary prevention strategies for coronary heart disease.

Widespread application of proven primary and secondary preventive strategies for coronary heart disease would result in substantial savings of life and health care dollars. Proven strategies (excluding lipid therapy) include quitting smoking, treating hypertension, physical activity, aspirin therapy, and appropriate use of anticoagulants, beta blockers, and angiotensin-converting enzyme inhibitors in survivors of myocardial infarction. Estrogen replacement therapy is currently under clinical investigation. Avoidance of obesity and tight control of diabetes are prudent interventions as yet unproved by clinical trials. Unfortunately, preventive strategies are frequently underutilized. The greatest challenge for preventive cardiology is to put into practice what we already know to prevent the development and progression of atherosclerosis.

Self-reported cardiac risk factors in emergency department nurses and paramedics.

STUDY OBJECTIVE: Our objective was to assess the prevalence of cardiac risk factors in a sample of urban paramedics and emergency department (ED) nurses. METHODS: We asked 175 paramedics and ED nurses working at a busy, urban ED to complete a cardiovascular risk assessment. The survey asked subjects to report smoking history, diet, exercise habits, weight, stress levels, medication use, history of hypertension or cardiac disease, family history of cardiovascular disease (CVD), and cholesterol level (if known). RESULTS: 129 of 175 surveys were returned (74% return rate) by 85 paramedics and 44 nurses. The percentages of paramedics and nurses at high or very high risk for cardiac disease were 48% and 41%, respectively. Forty-one percent of female respondents and 46% of male respondents were at high or very high risk. Cigarette smoking was reported in 19% of the paramedics and 14% of the nurses. The percentages of paramedics and nurses who reported hypertension were 13% and 11%, respectively. High cholesterol was reported in 31% of paramedics and 16% of nurses. CONCLUSIONS: Forty-eight percent of paramedics and 41% of ED nurses at this center are at high or very high risk for cardiovascular disease, by self-report. Efforts should be made to better educate and intervene in this population of health-care providers in order to reduce their cardiac risk.

Suggestions for teaching and evaluating a course in community dentistry.

A new approach to the teaching of behavioral sciences has been evaluated with one class of dental students. The findings suggest that educational environment and perceived qualities of instructor supportiveness are essential to the effectiveness of a socially oriented educational program.

Percutaneous coronary intervention versus medical therapy for coronary heart disease.

Medical therapy reduces myocardial infarction and death in patients with stable coronary heart disease (CHD). In contrast, there is little evidence available to evaluate the impact of percutaneous coronary intervention (PCI) on hard endpoints in such patients. Four randomized, controlled trials have compared PCI with medical therapy. These studies have demonstrated that PCI results in an improvement in angina and exercise tolerance compared with medical therapy, but they also suggest that medical therapy may be preferable to PCI with respect to the risk of cardiac events. Interpretation of these studies has been limited by small sample size, exclusion of high-risk subjects, no or reduced use of stents, lack of a cost- effectiveness evaluation, and absence of risk factor intervention (except for Atorvastatin versus Revascularization Treatment, which used aggressive low-density lipoprotein lowering with atorvastatin in the medical group only). The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial will permit better definition of the role of PCI in the treatment of stable or recently stabilized patients with CHD.

Preventive medicine in practice: the state of the art.

Primary and secondary prevention, as opposed to tertiary prevention, is the logical approach to attack today's leading causes of premature death. To apply preventive medicine in their practices, physicians may use a number of tools. The traditional annual examination should be abandoned in favor of periodic screening of asymptomatic patients according to age and sex. Screening should be done on a case-finding basis, facilitated by use of a longitudinal screening flow sheet and evaluated by use of a retrospective audit. An age-sex register can help identify which patients belong to a high-risk group. Health hazard appraisal is a tool for estimating a patient's risk before and after prescribed preventive intervention, and may stimulate patient risk factor reduction-as may other behavior modification techniques. In many cases these tools can be applied by paramedical personnel. Further research is needed to gauge the effects of these techniques on risk, morbidity and mortality.

Nicotine yield and measures of cigarette smoke exposure in a large population: are lower-yield cigarettes safer?

We examined the relationship of machine-estimated nicotine yield by cigarette brand with the level of cigarette consumption and two biochemical measures of smoke exposure (expired-air carbon monoxide and plasma thiocyanate) in a large, population-based sample of smokers (N = 713). The lower the nicotine yield of the cigarette, the greater the number of cigarettes smoked per day. Prior to adjusting for number of cigarettes smoked per day, nicotine yield was not related to the actual measures of smoke exposure. Smokers of ultralow-yield cigarettes had laboratory tests of smoke exposure which were not significantly different from those of smokers of higher-yield brands. Only after adjustment for number of cigarettes smoked per day did nicotine yield become significantly related to expired-air carbon monoxide and to plasma thiocyanate. In multivariate analysis, the number of cigarettes smoked per day accounted for 28 per cent and 22 per cent of the variance in observed expired-air carbon monoxide and plasma thiocyanate levels, respectively, whereas nicotine yield accounted for only 1 per cent and 2 per cent of the variance, respectively. The relative lack of an effect of nicotine yield on the biochemical measure appears to be due to the fact that smokers of lower nicotine brands smoked more cigarettes per day, thereby compensating for reduced delivery of smoke products. Our data do not support the concept that ultralow-yield cigarettes are less hazardous than others. Machine estimates suggesting low nicotine yield underrepresent actual human consumption of harmful cigarette constituents.

Temporal representation of clinical algorithms using expert-system and database tools.

The HyperLipid Advisory System combines a rule-based implementation of a clinical algorithm (the NIH Cholesterol Education Program Expert Panel recommendations) with a temporal representation that facilitates reasoning over time while maintaining efficient storage in a standard database. The temporal representation consists of objects that model point events such as visits and interval events such as specific therapies. These objects are combined into abstractions called phases, which correspond to higher level clinical concepts such as a diet or drug treatment. The time-oriented data objects are referenced in the rules using a custom-tailored operator query language. Between user sessions relevant clinical data are stored in external files. When the advisory system is reconsulted, this information is retrieved and mapped back into an object-oriented format. Use of a commercially available expert-system shell for such tasks allows algorithm implementation in standard personal computing environments.

Detection and classification of mutagens: a set of base-specific Salmonella tester strains.

A detection and classification system for mutagens has been developed that identifies the six possible base-pair substitution mutations. A set of six Salmonella typhimurium (TA7001 to TA7006) strains has been constructed, each of which carries a unique missense mutation in the histidine biosynthetic operon. In addition to the his mutation, these strains carry different auxiliary features that enhance the mutability of the target his mutation. These include the R factor pKM101, which has the SOS-inducible mucAB system; a deletion of the uvrB component of excision repair; and rfa mutations to increase the accessibility of bulky chemicals to the bacteria. Another set of strains (TA7041 to TA7046) contain a wild-type rfa gene. Reversion via the base substitution unique to each strain was verified by sequence analyses of > 800 revertants obtained from different types of mutagens. The strains have considerably lower spontaneous reversion frequencies and detect a variety of mutagens at a sensitivity comparable to the Salmonella tester strains TA100, TA102, and TA104. The low spontaneous frequency of reversion of a mixture of the six tester strains (approximately 10 revertants per plate) enables a single mutation assay with the mixture that is followed by classification of the type of mutation with the individual strains.

Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff.

BACKGROUND: To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS: After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS: These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.

[Tomodensitometric study of the course of supratentorial malignant glioma after treatment]. / Etude tomodensitométrique de l'évolution des gliomes malins sus-tentoriels après traitement.

Computed tomography now is the primary method for the management of supratentorial malignant gliomas. In this study, analysis of CT scan controls done at 2 or 3 month intervals in 87 treated patients showed that: 1) in most instances, recurrence arose within the initial tumor site; 2) the tumor invades contiguous anatomical structures through intra-and inter-hemispheric association fibers; 3) multicentric gliomas are uncommon (less than 6% of patients). The purpose of this study was to reduce irradiated volumes and thus radiation toxicity. The finding that most patients experience recurrence within the original tumor site is evidence experience recurrence within the original tumor site is evidence that current radiation doses and total brain irradiation are inappropriate. Our results are consistent with those recently reported in the medical literature. Using computed tomography data, it should be possible to restrict the irradiated volume to the tumor site and to presumptive extension pathways. Higher doses may be delivered to this volume.

Depressive symptoms and substance use among adolescent binge eaters and purgers: a defined population study.

We surveyed 646 tenth grade females in Northern California to assess the prevalence of binge eating and purging behaviors. Of these, 10.3 per cent met study criteria for bulimia and an additional 10.4 per cent reported purging behaviors for weight control. Bulimics and purgers were heavier, had greater triceps and subscapular skinfold thicknesses, and reported higher rates of drunkenness, marijuana use, cigarette use, and greater levels of depressive symptomatology.