Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.     

Elevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation

PurposeWe aimed to assess the prognostic value of Neutrophil to Lymphocyte Ratio (NLR) on long-term outcomes and graft dysfunction after lung transplantation.MethodsWe retrospectively reviewed all patients receiving a lung transplant at our institution from 2011 to 2014. The primary exposure was elevated NLR at the time of transplant, defined by NLR>4. The primary outcomes were graft failure and three-year all-cause mortality. Multivariate logistic regression and Kaplan-Meier survival analysis were used to analyze outcomes.Results95 patients were included. 40 patients (42%) had an elevated NLR. Elevated NLR was associated with graft failure (OR: 4.7 [1.2–18.8], p = 0.02), and three-year mortality (OR: 5.4 [1.3–23.2], p = 0.03) on multivariate logistic regression. Patients with elevated NLR demonstrated significantly lower survival on Kaplan-Meier analysis (50% versus 74%, p = 0.02). The c-statistic for our multivariate model was 0.91.ConclusionElevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation.     

Two screening instruments for collecting alcohol-related information from expectant mothers and fathers: Testing the reliability of the Parent Alcohol Screening Questionnaire and the Social Support for an Alcohol-Free Pregnancy Questionnaire

The aim is to test the reliability of two alcohol screening instruments: (1) The Parent Alcohol Screening Questionnaire (PASQ5), and (2) the Social Support for an Alcohol-free Pregnancy (SSAFP) questionnaire. This is a cohort study from the south of Sweden using repeated surveys during pregnancy. To examine if responses differed according to different data collection methods, two cohorts consisting of 289 expectant mothers and 141 fathers completed the PASQ5 both verbally (weeks 6–7) and in writing (week 12) within regular antenatal visits. One of the cohorts (n = 137/64) also completed the SSAFP in week 12 and later in week 33. The third cohort, consisting of 179 and 133 expectant mothers and fathers, respectively, completed the PASQ5 and the SSAFP twice in late pregnancy (week 31 + 33). Eight of 10 items in the PASQ5 were stable for both expectant mothers and expectant fathers when comparing verbal versus written-delivered formats. Eight of 10 questions in the PASQ5 were stable when assessing the items in a test–retest analysis in late pregnancy for expectant mothers and nine of 10 questions were stable for fathers. The SSAFP items showed high internal consistency (0.86) for expectant mothers and excellent internal consistency (0.94) for expectant fathers. Most SSAFP items (17 of 21 for expectant mothers and 18 of 22 for expectant fathers) were also stable in a test–retest scenario in late pregnancy. Both the PASQ5 and SSAFP are reliable tools and may be helpful for clinicians who aim to have a deeper dialogue about alcohol consumption during pregnancy. These tools may also be helpful for researchers aiming to better understand a person's changes in alcohol intake and/or their social support network.     

Evidence for an Interaction Between the β-Blocker Pafenolol and Bile Salts in the Intestinal Lumen of the Rat Leading to Dose-Dependent Oral Absorption and Double Peaks in the Plasma Concentration–Time Profile

Pafenolol is a -blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile.     

Androgen treatment of abdominally obese men

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.     

Diagnostic outcome of repeated mammography screening

Mammographic screening for breast cancer within health service routines was evaluated for the years 1987–1992, with special focus on repeated screening during 1989–1992. The overall attendance rate by women aged 40 to 74 years was 82.8%. During 1989–1992 malignancy was found in 2.6/1000 screened women, giving a 87.4% positive predictive rate at surgery and 95.9% efficiency. Among women aged 45, the positive predictive rate was >94%. Fine-needle aspiration (FNA) biopsy showed invasive cancers in 84% and highly suspected cancer in another 15%; 60% of the lesions were nonpalpable. For first-time (prevalence) screening (1987–1988) the positive predictive rate was 86% and the malignancy yield 6.4/1000. In women aged 40–44 years there were few surgical referrals (1.6%), but the positive predictive rate at surgery was only 48.3%, indicating diagnostic difficulties in young women. The median size of all invasive cancers was 12 mm: 84% were classified as pT1, and 23% had lymph node involvement. Stage II disease was found in 27% of all malignancies. The use of FNA in the diagnostic workup for breast cancer screening is of crucial importance to the maintenance of high positive predictive rates at surgery. Moreover, regular analysis is important even when mammographic screening is incorporated into the routine work of health services.

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Resumen El tamizaje mamográfico para cáncer del seno como parte de las rutinas de los servicios de salud fue evaluado para los años 1987–1992, con especial énfasis en el tamizaje repetido en el período 1989–1992. La tasa de cumplimiento por parte de las pacientes en las edades 40–74 años fue de 82.8%. En 1989–92 se halló neoplasia maligna en 2.6/1000 mujeres tamizadas, lo cual significó un índice de predicción de positividad en la cirugía de 87.4% y de eficiencia de 95.9%. Entre las mujeres con edad 45 años el valor de predicción de positividad fue >94%. La biopsia por aspiración con aguja fina demostró cánceres invasores en 84% y alta sospecha de cáncer en un 15% adicional; 60% de las lesiones fueron no palpables. En el tamizaje de primera vez (prevalencia, 1987–1988) el valor de predicción de positividad fue de 86% y el rendimiento de 6.4/1000. En las mujeres con edades 40–44 años se hicieron menos referencias para cirugía (1.6%) pero el valor de predicción de positividad en la cirugía fue apenas de 48.3%, lo cual indica dificultades diagnósticas en las pacientes más jóvenes. El tamaño promedio de los cánceres invasores fue 12 mm; 84% fueron clasificados como pT1 y 25% presentaban invasión ganglionar; 27% de todos los tumores malignos fueron estado II. La aspiración con aguja fina en la evaluación diagnóstica del tamizaje para cáncer mamario es de importancia crucial para el mantenimiento de un alto valor de predicción de positividad en la cirugía y el análisis regular es importante aun cuando el tamizaje mamográfico quede incorporado en el trabajo rutinario de los servicios de salud.

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Résumé Le dépistage systématique des cancers du sein par mammographie effectuée par les services de santé a été évalué entre 1987–1992, en particulier le dépistage répété pratiqué entre 1989–1992. Le taux de participation des femmes âgées entre 40–74 ans a été de 82.8%. Dans la période 1989–1992, une tumeur maligne a été retrouvée chez 2.6/1000 femmes, la chirurgie permettant de calculer une valeur prédictive positive de 87.4% et une efficacité de 95.9%. Chez les femmes âgées de plus de 45 ans, la valeur prédictive positive a dépassé 94%. La ponction biopsie a fourni la preuve de cancer invasif dans 84% des cas et celle d'une forte suspicion dans 15% des cas, alors que 60% des lésions n'étaient pas palpables. Par comparaison, la valeur prédictive positive pendant la période de dépistage entre 1987–88 a été de 96% pour une prévalence de cancer de 6.4/1000. Chez la femme âgée entre 40–44 ans, très peu de femmes ont été opérées, avec une valeur prédictive positive de 48.3%, ce qui démontre les difficultés de diagnostic chez la femme jeune. La taille médiane de tous les cancers invasifs était de 12 mm: 84% étaient classés comme pT1 et 23% avaient un envahissement lymphatique. On a trouvé un stade II chez 27% des patientes tous cancers confondus. L'utilisation de ponction biopsie est capitale pour le diagnostic de cancer de sein pour maintenir une valeur prédictive positive élevée lors de la chirurgie et une analyse régulière est nécessaire même lorsque le dépistage systématique par mammographie est inclu dans le programme des service de santé.

     

Within-day variability of magnetic fields among electric utility workers: consequences for measurement strategies

Occupational exposure to 50-Hz magnetic fields was surveyed among electric utility workers to investigate (1) components of exposure variability, (2) patterns of autocorrelation between short-term measurements, and (3) imprecision and misclassification due to short-term measurements. Spot measurements every 10 seconds during 81 working days were analyzed for 42 electric utility workers from 10 occupational subgroups and during 8 working days for 4 office workers from the same company. For the 8-hour time-weighted average (TWA) magnetic fields, the variability was partitioned into its components: within workers, between workers, and between groups. For spot measurements of magnetic fields, the within-day variance component also was examined. Autocorrelation functions were determined and numbers of short-term measurements necessary for reliable estimates of 8-hour TWA magnetic fields were assessed. Spot measurements of magnetic fields, as well as 8-hour TWA magnetic fields, were approximately log normally distributed among workers. The mean exposure to magnetic fields was 0.47 microT (n = 81 days) in electric utility workers and 0.12 microT (n = 8 days) in office workers. A large fraction, 76% of the spot measurements total variance, could be attributed to variability within days. For the 8-hour TWA magnetic fields, between-group variability was small and of the same magnitude as between-worker variability. Significant autocorrelations between short-term averages of 7.5, 15, and 30 minutes were present, when taken within periods of 30 minutes. One-hour averages showed no autocorrelation. Simulations showed that, due to high within-day variability and autocorrelation, a limited number of short-term measurements of magnetic fields in electric utility workers are likely to result in imprecise estimates of 8-hour TWA magnetic fields. Measurement strategies relying on short-term (spot) measurements are therefore likely to result in misclassification of exposure and consequently absent or spurious exposure-response relations.     

Persistent Organochlorines in the Effluents from a Chlorine-Bleached Kraft Integrated Pulp and Paper Mill in Southeast Asia

A bleached sulfate integrated pulp and paper mill producing printing and writing paper from mixed tropical hardwood and bamboo was studied. The mill uses a “conventional bleaching sequence,” C-E-H1-H2, with an average molecular chlorine consumption of 50 kg per ton of air-dried pulp (ADP). The content of polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) in the bleaching filtrate in terms of the nordic toxicity equivalent (N-TEQ) was 33.5, 1.15, 0.56, and 0.014 pg/L for the E, C, H1, and H2 bleaching stages, respectively. The corresponding PCDFs and PCDDs loads in ng/t ADP were in the same ranking, i.e., 670, 69, 11.2, and 0.28, respectively. The congener and isomeric pattern of PCDFs and PCDDs of the bleaching filtrate and the bleached pulp was found to be typical for the chlorine bleaching plant effluent. The obtained dioxin load formed in the mill is in agreement with Western studies for the given multiple chlorine of 0.21–0.23. The load is, however, lower than reported discharges from Scandinavian mills using 1980s bleaching technologies, but substantially higher than the discharges from mills with modern bleaching technologies. Modifications in the bleaching plant to reduce molecular chlorine use are necessary to reduce dioxin formation. Received: 15 July 1998/Accepted: 17 March 1999