Quantitative food web modeling unravels the importance of the microphytobenthos-meiofauna pathway for a high trophic transfer by meiofauna in soft-bottom intertidal food webs.

Meiofauna are known to have an important role on many ecological processes, although, their role in food web dynamics is often poorly understood, partially as they have been an overlooked and under sampled organism group. Here, we used quantitative food web modeling to evaluate the trophic relationship between meiofauna and their food sources and how meiofauna can mediate the carbon flow to higher trophic levels in five contrasting soft-bottom intertidal habitats (including seagrass beds, mudflats and sandflats). Carbon flow networks were constructed using the linear inverse model-Markov chain Monte Carlo technique, with increased resolution of the meiofauna compartments (i.e. biomass and feeding ecology of the different trophic groups of meiofauna) compared to most previous modeling studies. These models highlighted that the flows between the highly productive microphytobenthos and the meiofauna compartments play an important role in transferring carbon to the higher trophic levels, typically more efficiently so than macrofauna. The pathway from microphytobenthos to meiofauna represented the largest flow in all habitats and resulted in high production of meiofauna independent of habitat. All trophic groups of meiofauna, except for selective deposit feeders, had a very high dependency on microphytobenthos. Selective deposit feeders relied instead on a wider range of food sources, with varying contributions of bacteria, microphytobenthos and sediment organic matter. Ecological network analyses (e.g. cycling, throughput and ascendency) of the modeled systems highlighted the close positive relationship between the food web efficiency and the assimilation of high-quality food sources by primary consumers, e.g. meiofauna and macrofauna. Large proportions of these flows can be attributed to trophic groups of meiofauna. The sensitivity of the network properties to the representation of meiofauna in the models leads to recommending a greater attention in ecological data monitoring and integrating meiofauna into food web models.

Giant cell tumors of the sacrum--a nationwide study on midterm results in 26 patients after intralesional excision.

PURPOSE: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). METHODS: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan-Meier, Cox regression, log rank and Mann-Whitney U. RESULTS: Recurrence rate was 14/26 after median 13 (3-139) months and was highest after isolated curettage (4/5). Soft tissue masses >10 cm increased recurrence risk (HR = 3.3, 95 % CI = 0.81-13, p = 0.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; p = 0.024). CONCLUSION: Recurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.

Tracked ultrasound registration for intraoperative navigation during pediatric bone tumor resections with soft tissue components: a porcine cadaver study.

PURPOSE: Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model. METHODS: First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire. RESULTS: Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work. CONCLUSION: The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up.

OBJECTIVES: In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re-evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia. METHODS: This was a retrospective review of the records of 30 consecutive fetuses with tachycardia documented on M-mode echocardiography between January 2004 and December 2010 at Wilhelmina Children's Hospital, a tertiary referral university hospital. Patients were subdivided into those diagnosed with supraventricular tachycardia and those with atrial flutter (AF) and presence of hydrops was noted. Other variables investigated included QTc interval measured on maternal electrocardiogram before and after initiation of antiarrhythmic therapy, fetal heart rhythm and heart rate pre- and postnatally, oral maternal drug therapy used, time to conversion to sinus rhythm (SR), percentage of fetuses converted following transplacental treatment, maternal adverse effects, presence or absence of tachycardia as noted on postnatal ECG, postnatal therapy or prophylaxis and neonatal outcome. Findings are discussed with reference to the literature. RESULTS: A total of 28 patients (18 with SVT, 10 with AF) were treated with sotalol as first-line therapy. Fetal hydrops was present in six patients (five with SVT, one with AF). All hydropic patients converted antenatally to SR (67% with sotalol as a single-drug therapy, 33% after addition of flecainide). Of the non-hydropic patients, 91% converted to SR (90% with sotalol only, 10% after addition of flecainide or digoxin). In 9% (with AF) rate control was achieved. There was no mortality. No serious drug-related adverse events were observed. Postnatally, rhythm disturbances were detected in 10 patients, two of whom still had AF. In eight, SVT was observed within 3 weeks postnatally, and in five of these within 72 hours. CONCLUSIONS: Sotalol can be recommended as the drug of first choice for treatment of fetal AF and has been shown to be an effective and safe first-line treatment option for SVT, at least in the absence of hydrops. Postnatal maintenance therapy after successful prenatal therapy is not necessarily indicated, as the risk of recurrence is low beyond 72 hours of age.

Characterization of denosumab treatment response in giant cell tumors of bone with dynamic contrast-enhanced MRI.

RATIONALE AND OBJECTIVES: Denosumab is a monoclonal antibody used neo-adjuvantly in giant cell tumor of bone (GCTB) to facilitate surgery, or long term for axial tumors where surgery comes with high morbidity. Time intervals for treatment effects to occur are unclear and monitoring tools are limited, complicating optimal drug dose titration. We assessed changes in time intensity curve (TIC) - derived perfusion features on DCE-MRI in GCTB during denosumab treatment and evaluated the duration of treatment effects on tumor perfusion. MATERIALS AND METHODS: Patients with GCTB who underwent dynamic contrast enhanced (DCE) MRI before (t = 0) and after 3 (t = 3), 6 (t = 6) or 12 (t = 12) months of denosumab treatment were retrospectively included in a single center. Regions of interest were placed on tumor compartments with visually most intense enhancement and TICs were created. Time-to-enhancement (TTE), wash-in rate (WIR), maximal relative enhancement (MRE), and area-under-the-curve (AUC) were calculated. Differences in perfusion features were calculated with the Wilcoxon signed-rank test. RESULTS: In all 24 patients decreased perfusion on DCE-MRI after start of denosumab treatment was seen. TTE increased between t = 0 and t = 3 (p < 0.001). WIR, MRE and AUC decreased between t = 0 and t = 3 (p < 0.001, p = 0.01 and p = 0.02, respectively). No significant differences in features were found between t = 3 and t = 6 or t = 6 and t = 12. No significant perfusion differences in primary versus recurrent, or axial versus appendicular tumors, were found. CONCLUSION: MRI perfusion significantly changed in GCTB within 3 months of denosumab treatment compared to baseline. No further significant change occurred between 3 and 6, and 6 and 12 months of treatment. These findings suggest that evaluation of treatment response and subsequent consideration of maintenance with lower doses of denosumab, may already be indicated after 3 months. In cases where long term denosumab is the preferred therapy, monitoring change in tumor characteristics on DCE-MRI may aid optimal drug dose titration, minimizing side effects.

The use of microtracers in food-effect trials: An alternative study design for toxic drugs with long half-lives exemplified by the case for alectinib.

The traditional design of food-effect studies has a high patient burden for toxic drugs with long half-lives (e.g., anticancer agents). Microtracers could be used to assess food-effect in patients without influencing their ongoing treatment. The feasibility of a microtracer food-effect study during steady-state of the therapeutic drug was investigated in an in silico simulation study with alectinib as an example for a relative toxic drug with a long half-life. Microtracer pharmacokinetics were simulated based on a previously published population pharmacokinetic model and used for estimation of a model with and a model without food as a covariate on oral bioavailability of alectinib (assuming a 40% food-effect). Power was defined as the fraction of clinical trials where a significant (p < 0.01) food-effect was identified. The proposed study design of 10 patients on steady-state treatment, 10 blood samples collected within 24 h after administration and an assumed food-effect of 40% had a power of 99.9%. The mean estimated food-effect was 39.8% (80% confidence interval: 31.0%-48.6%). The feasibility of microtracer food-effect studies was demonstrated. The design of the microtracer food-effect study allowed estimation of the food-effect with minimal influence on therapeutic treatment and reducing patient burden compared to the traditional study design for toxic drugs with long half-lives.

Soft tissue extension increases the risk of local recurrence after curettage with adjuvants for giant-cell tumor of the long bones.

BACKGROUND AND PURPOSE: Risk factors for local recurrence of giant-cell tumor of bone (GCTB) have mostly been studied in heterogeneous treatment groups, including resection and intralesional treatment. The aim of the study was the identification of individual risk factors after curettage with adjuvants in GCTB. METHODS: Of 147 patients treated for primary GCTB between 1981 and 2009, 93 patients were included in this retrospective single-center study. All patients were treated with curettage and polymethylmethacrylate (PMMA) with (n = 75) or without (n = 18) phenol. Mean follow-up was 8 (2-24) years. Recurrence-free survival was assessed for treatment modalities. Age, sex, tumor location, soft tissue extension, and pathological fractures were scored for every patient and included in a Cox regression analysis. RESULTS: The recurrence rate after the first procedure was 25/93. Recurrence-free survival for PMMA and phenol and for PMMA alone was similar. Eventually, local control was achieved using 1 or multiple intralesional procedures in 85 patients. Resection was required in 8 patients. A higher risk of local recurrence was found for soft tissue extension (HR = 5, 95% CI: 2-12), but not for age below 30, sex, location (distal radius vs. other), or pathological fracture. INTERPRETATION: Curettage with adjuvants is a feasible first-choice treatment option for GCTB, with good oncological outcome and joint preservation. Soft tissue extension strongly increased the risk of local recurrence, whereas age, sex, location, and pathological fractures did not.

Malignant Transformation of Giant Cell Tumor of Bone and the Association with Denosumab Treatment: A Radiology and Pathology Perspective.

Objective: Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy. Methods: From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB. Results: At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2-11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component. Conclusion: In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB.

A highly sensitive bioanalytical method for the quantification of vinblastine, vincristine, vinorelbine and 4-O-deacetylvinorelbine in human plasma using LC-MS/MS.

A highly sensitive method was developed for the quantification of vinblastine, vincristine, vinorelbine, and its active metabolite 4-O-deacetylvinorelbine in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterated isotopes were used as internal standard and liquid-liquid extraction with tert-butyl methyl ether (TBME) was used for sample pre-treatment. The final extract was injected on a C18 column (50 × 2.1 mm ID, 5 µm). Gradient elution was used in combination with Reversed Phase chromatography to elute the analytes and internal standards from the column in 5 min and the API4000 triple quadrupole MS detector was operating in the positive ion mode. The calibration model, accuracy and precision, selectivity and specificity, dilution integrity, carryover, matrix factor and recovery, and stability were evaluated over a concentration range from 0.025 to 10 ng/mL for vinblastine, vinorelbine, and 4-O-deacetylvinorelbine and from 0.1 to 40 ng/mL for vincristine. The intra- and inter-assay bias and precisions were within ± 12.4% and ≤ 10.6%, respectively. This method was successfully applied to study the pharmacokinetics of vincristine in paediatrics and vinorelbine and 4-O-deacetylvinorelbine using in vivo mouse models.

Highly Variable Paracetamol Pharmacokinetics After Multiple Oral Dosing in Frail Older People: A Population Pharmacokinetic Analysis.

INTRODUCTION: Paracetamol pharmacokinetics (PK) is highly variable in older fit adults after intravenous administration. Frailty and oral administration likely result in additional variability. The aim was to determine oral paracetamol PK and variability in geriatric inpatients. METHODS: A population PK analysis, using NONMEM 7.2, was performed on 245 paracetamol samples in 40 geriatric inpatients (median age 87 [range 80-95] years, bodyweight 66.4 [49.3-110] kg, 92.5% frail [Edmonton Frail Scale]). All subjects received paracetamol 1000 mg as tablet (72.5%) or granulate (27.5%) three times daily. Simulations of dosing regimens (1000 mg every 6 hours [q6h] or q8h) were performed to determine target attainment, using mean steady-state concentration (Css-mean) of 10 mg/L as target. RESULTS: A one-compartment model with first order absorption and lag time best described the data. The inter-individual variability was high, with absorption rate constant containing the highest variability. The inter-individual variability could not be explained by covariates. Simulations of 1000 mg q6h and q8h resulted in a Css-mean of 10.8 [25-75th percentiles 8.2-12.7] and 8.13 [6.3-9.6] mg/L, respectively, for the average geriatric inpatient. The majority of the population remained off-target (22.2% [q6h] and 52.2% [q8h] <8 mg/L; 31.3 [q6h] and 7.6% [q8h] >12 mg/L). CONCLUSION: A population of average geriatric inpatients achieved target Css-mean with paracetamol 1000 mg q6h, while q8h resulted in underexposure for the majority of them. Due to high unexplained variability, a relevant proportion remained either above or below the target concentration of 10 mg/L. Research focusing on PK, efficacy and safety is needed to recommend dosing regimens.

Trophic importance of microphytobenthos and bacteria to meiofauna in soft-bottom intertidal habitats: A combined trophic marker approach.

Meiofauna can play an important role in the carbon fluxes of soft-bottom coastal habitats. Investigation of their feeding behavior and trophic position remains challenging due to their small size. In this study, we determine and compare the food sources used by nematodes and benthic copepods by using stable isotope compositions, fatty acid profiles and compound specific isotope analyses of fatty acids in the mudflats, seagrass beds and a sandflat of the Marennes-Oléron Bay, France, and the Sylt-Rømø Bight, Germany. Suspended particulate organic matter was much more 13C-depleted than other food sources and meiofauna, highlighting its poor role in the different studied habitats. The very low proportions of vascular plant fatty acid markers in meiofauna demonstrated that these consumers did not rely on this food source, either fresh or detrital, even in seagrass beds. The combined use of stable isotopes and fatty acids emphasized microphytobenthos and benthic bacteria as the major food sources of nematodes and benthic copepods. Compound specific analyses of a bacteria marker confirmed that bacteria mostly used microphytobenthos as a substrate.

Maintenance interventions for overweight or obesity in children: a systematic review and meta-analysis.

Childhood obesity is associated with significant health consequences. Although several intervention programmes for children result in weight loss or stabilization in the short-term, preventing relapse after treatment remains an important challenge. This systematic review summarizes the evidence about maintenance interventions after treatment in childhood obesity. Studies were identified by searching PubMed, Embase, Cochrane Library, Scopus, Web of Science, PsycINFO, CINAHL and SocINDEX. The primary outcome measure for this review was body mass index standard deviation score (BMI-Z-score). Data were pooled using quality effect models. Eleven studies (1,532 participants, age 2-18 years) were included, covering a wide range of maintenance approaches. Included studies varied widely in methodological quality. Pooled analysis showed that the BMI-Z-score of maintenance intervention participants remained stable, whereas control participants experienced a slight increase. No differences were observed regarding intensity and duration of therapy. A slight preference for 'face-to-face' versus 'on distance' interventions was shown. In summary, this review shows that, although there is limited quality data to recommend one maintenance intervention over another, continued treatment does have a stabilizing effect on BMI-Z-score. Considering the magnitude of the problem of childhood obesity, this is an important finding that highlights the need for further research on weight loss maintenance.

Hormonal regulation of phospholipase D activity in Ca(2+) transporting cells of rabbit connecting tubule and cortical collecting duct.

Phospholipase D (PLD) is distributed widely in mammalian tissues where it is believed to play an important role in the regulation of cell functions and cell fate by a variety of extracellular signals. In this study, we used primary cultures of rabbit connecting tubule (CNT) and cortical collecting duct (CCD) cells, grown to confluence on a permeable support, to investigate the possible involvement of PLD in the mechanism of action of hormones that regulate Ca(2+) reabsorption. RT-PCR revealed the presence of transcripts of PLD1b and PLD2, but not PLD1a, in these cultures. Moreover, the expression of substantial amounts of PLD1 protein was demonstrated by Western blotting. To measure PLD activity, cells were labelled with [(3)H]myristic acid after which the PLD-catalysed formation of radiolabelled phosphatidylethanol ([(3)H]PtdEth) was measured in the presence of 1% (v/v) ethanol. Deamino-Cys,D-Arg(8)-vasopressin (dDAVP) and N(6)-cyclopentyladenosine (CPA), two potent stimulators of Ca(2+) transport across these monolayers, stimulated PLD activity as was indicated by a marked increase in [(3)H]PtdEth. Similarly, ATP, a potent inhibitor of dDAVP- and CPA-stimulated Ca(2+) transport, increased the formation of [(3)H]PtdEth. PLD activity was furthermore increased by 8Br-cAMP and following acute (30 min) stimulation of protein kinase C (PKC) with a phorbol ester (PMA). Chronic PMA treatment (120 h) to downregulate phorbol ester-sensitive PKC isoforms did not affect PLD activation by dDAVP, CPA and 8Br-cAMP, while markedly decreasing the effect of ATP and abolishing the effect of PMA. The PKC inhibitor chelerythrine significantly reduced PLD activation by dDAVP, CPA and 8Br-cAMP, without changing the effect of ATP. The inhibitor only partially reduced the effect of PMA. This study shows that Ca(2+) transporting cells of CNT and CCD contain a regulated PLD activity. The physiological relevance of this activity, which is not involved in Ca(2+) reabsorption, remains to be established.

Calcium supplementation: effect on blood pressure and urinary mineral excretion in normotensive male lactoovovegetarians and omnivores.

After an initial 4-wk period, 36 healthy male subjects aged 19-28 y (14 lactoovovegetarians and 22 omnivores) were given a supplement to their usual diet of 27.9 mmol calcium/d for 5 wk. During this period 22 blood pressure measurements were taken and 30 24-h urine specimens and 15 24-h dietary records were obtained. Base-line blood pressures did not differ significantly between vegetarians and omnivores (118.3/59.3 and 119.5/60.7, respectively). At the end of the supplementation period there was a decrease in diastolic blood pressure of 1.4 mm Hg (p less than 0.10) and an unexpected increase in systolic blood pressure of 2.1 mm Hg (p less than 0.01) in the omnivores. Although not significant, the same trends were observed in the vegetarians. In both groups Ca and magnesium excretions increased significantly and phosphorus excretion decreased significantly. Blood pressure of normotensive subjects with high basal Ca intake may not be sensitive to Ca supplementation.

Effect of lactation on resting metabolic rate and on diet- and work-induced thermogenesis.

Energy metabolism was measured in 24 women before pregnancy and during lactation (2 mo postpartum). Resting metabolic rate (RMR) increased by 0.17 +/- 0.38 kJ/min and postprandial metabolic rate (PPMR) showed a similar increase (0.17 +/- 0.45 kJ/min). Thus, the thermic effect of the meal (PPMR minus RMR) was not affected by lactation. Between subjects, the lactation-induced increase in RMR appeared to be positively related to body weight. During lactation gross metabolic rates during cycling (CMR) were slightly reduced and net metabolic rates during cycling (CMR minus RMR) tended to decrease by 0.6 kJ/min at all workloads; however, the decrease was statistically significant only at the lowest workload. Changes in metabolic rate during the recovery period after exercise were not significant, but resembled changes in RMR rather than changes in CMR. We conclude that no major changes in metabolic efficiency occurred during lactation.

The effect of dietary sodium on urinary calcium and potassium excretion in normotensive men with different calcium intakes.

On the basis of their usual calcium intake, 12 healthy normotensive male students were divided into a low and a high calcium group. Both groups were provided with complete diets containing the same calculated quantities, expressed per MJ, of protein, fat, carbohydrate, sodium, potassium, phosphorus, and calcium. After an initial period of two weeks during which all participants received an additional 100 mmol sodium daily, 6 participants received an additional 22 mmol sodium/day (low sodium), the other 6 participants 178 mmol sodium/day (high sodium). After two weeks the sodium regimes were crossed over for a subsequent two-week period. When the second week of the low sodium period is compared with the second week of the high sodium period, the increase in the calcium/creatinine ratio, expressed on molar basis, was 0.059 for the low and 0.053 for the high calcium group (p less than 0.05). The increase in the molar potassium/creatinine ratio was 0.65 for the low and 0.03 for the high calcium group (p less than 0.025). However, after correcting for the calcium intake the effect in the low calcium group was found to be greater (p less than 0.05). Sodium supplementation was found to have no effect on blood pressure, but mean systolic (p less than 0.10) and diastolic in the high calcium group were lower. This suggests that calcium may well play a role in the regulation of blood pressure.

Energy balances of healthy Dutch women before and during pregnancy: limited scope for metabolic adaptations in pregnancy.

To investigate changes in energy metabolism during pregnancy, complete 8-d energy balances were measured before pregnancy and at 12, 23, and 34 wk gestation in 12 healthy Dutch women. While for each individual woman experimental diets were kept constant throughout the study with average intakes of 8.76 +/- 0.92 MJ/d (before pregnancy), 8.72 +/- 1.08 MJ/d (week 12), 8.85 +/- 0.93 MJ/d (week 23), and 8.72 +/- 1.12 MJ/d (week 34), neither the digestibility nor the metabolizability of the supplied diets showed significant changes from before pregnancy (92.8% and 88.6%, respectively) throughout pregnancy (92.7% and 88.2%, respectively). Twenty-four-hour energy expenditure (24-h EE) increased significantly from 8.63 +/- 0.80 MJ/d (before pregnancy) to 8.73 +/- 1.15, 9.08 +/- 1.08, and 9.94 +/- 0.94 MJ/d in weeks 12, 23, and 34 of gestation, to the extent predictable from changes in resting metabolic rate so that in an experimental setting with physical activity and energy intake standardized there seems little scope for other adaptive mechanisms.

Socioeconomic status and breast cancer survival in the southeastern Netherlands, 1980-1989.

Socioeconomic differences in breast cancer survival in the southeastern Netherlands between 1980 and 1989 were studied (n = 3928), as was the impact of prognostic factors (stage at diagnosis, morphology, and treatment) on such differences. An area-based measure of socioeconomic status (SES) in five groups, based on the postcode of residence at the time of diagnosis, was used. In univariate analyses the relative survival rate was used to correct for causes of death other than breast cancer. The measure of outcome in multivariate analyses was the hazard ratio. The results of both univariate and multivariate analyses suggested a small survival advantage for the higher SES groups. In a model with follow-up period, SES and age, the hazard ratios with 95% confidence intervals (CI) for SES groups from high to low were: 1.00, 1.06 (0.84-1.33), 1.04 (0.86-1.26), 1.15 (0.96-1.38), 1.18 (0.99-1.42). After a correction for stage at diagnosis, differences in survival were reduced substantially. Morphology and treatment were not important explanatory factors of the SES survival association. We conclude that small socioeconomic differences in breast cancer survival exist in The Netherlands and that stage at diagnosis is the most important determinant of such differences.

Comorbidity and colorectal cancer according to subsite and stage: a population-based study.

In developed countries the growing proportion of elderly colorectal cancer patients with comorbidity will probably complicate clinical management. The aim of this study was to investigate the prevalence of prognostically relevant comorbidity in unselected colorectal cancer patients diagnosed in the Eindhoven Cancer Registry, according to age, gender and subsite and the association with stage of disease, treatment and short-term survival. Comorbid conditions were recorded, according to Charlson's index. The most common concomitant illnesses were cardiovascular diseases, previous cancers and hypertension. The prevalence of comorbidity, especially of cardiovascular disease, previous cancer and diabetes, was highest in the ascending colon. It was slightly higher in patients with Dukes' stage A, probably due to early detection because of regular monitoring for the comorbid condition. Comorbidity was not associated with the resection rate, but was negatively associated with short-term survival. Elder male colorectal cancer patients particularly suffer from substantial comorbidity, influencing the prognosis.

Striking changes in smoking behaviour and lung cancer incidence by histological type in south-east Netherlands, 1960-1991.

Changes in lung cancer incidence in south-east Netherlands between 1960 and 1991 were analysed, using data from the Eindhoven Cancer Registry, and related to previous changes in smoking habits. Male lung cancer incidence rates increased markedly from birth cohorts 1890-1899 to 1910-1919, followed by a decline. The peak incidences for both squamous cell carcinoma and small cell carcinoma were reached in 1978, while for adenocarcinoma it was 1985. A rising trend in female lung cancer incidence up to 1988 was found for each successive birth cohort and for every histological type. These changes in lung cancer incidence rates are most likely related to the pattern of past smoking habits: the percentage of male adult smokers in the southern part of the Netherlands decreased from 95% in 1960 to 40% in 1981 and the percentage of female adult smokers increased from 27% in 1960 to 40% in 1967, slightly decreasing only after 1979. In view of the trends in smoking behaviour, the incidence rates for male lung cancer will decline further, whereas female lung cancer incidence may decrease after the year 2000.