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Objective: To report Australian outcomes from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR).Design: Observational study using data collected prospectively from December 2002 to December 2008.Setting: Centres administering thrombolysis for acute stroke in Australia and worldwide.Patients: All patients treated with recombinant tissue plasminogen activator for acute stroke in participating centres, regardless of stroke severity, time of treatment and other clinical factors.Intervention: Thrombolysis for acute stroke, administered according to local protocol.Main Outcome Measures: Functional outcome as 3-month modified Rankin score (mRS), and frequency of symptomatic intracerebral haemorrhage (ICH).Results: During the study period, a total of 32 countries participated, and confirmed baseline data were available for 581 Australian patients and 20 953 patients in the rest of the world. Australian patients were older (median age, 73 v 69 years; P < 0.001), were less independent before stroke (premorbid mRS of 0-1, 87.5% v 91.2%; P < 0.005), and had more comorbidities and more severe strokes. Comparing the Australian cohort with the rest of the world, the odds ratio of 3-month mRS of 0-2 was 0.98 (95% CI, 0.88-1.08; P = 0.63), the odds ratio of symptomatic ICH was 0.98 (95% CI, 0.83-1.16; P = 0.85 [by the definition used by the National Institute of Neurological Disorders]) and the odds ratio of death was 1.04 (95% CI, 0.91-1.19; P = 0.54). Good outcome in the Australian cohort was predicted by younger age, presence of hyperlipidaemia, lower premorbid mRS, absence of infarct on early brain imaging, less severe stroke, and lower baseline blood glucose level.Conclusion: Clinical outcomes after thrombolysis in Australia were similar to those worldwide. [ABSTRACT FROM AUTHOR]

Introduction: Brief cognitive tests such as the Mini-mental State Examination (MMSE) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) have been used to detect cognitive impairment and dementia in studies of stroke patients. However, there are few data on their validity for such use. We have evaluated their validity in detecting cognitive impairment not dementia (CIND) and dementia in a community-based sample of first-ever stroke patients.Methods: The standardized MMSE (S-MMSE) and the 16-item IQCODE were administered to 79 patients 1 year after a first-ever stroke. CIND and dementia were diagnosed independently using a comprehensive cognitive battery. The performances of the two tests were evaluated using receiver operating characteristic (ROC) analyses. Combined performance was evaluated when their scores were used in parallel (the "or rule"), in series (the "and rule") or as a weighted sum (the "weighted sum rule").Results: Both tests were extremely poor at detecting CIND individually and in combination. For dementia, at traditional cut-points, the S-MMSE (< or =23) was insensitive (0.50, 95% CI 0.16-0.84) and the IQCODE (> or =3.30) nonspecific (0.63, 95% CI 0.51-0.75). An acceptable balance between sensitivity and specificity was achieved for dementia using the "or rule" combination, but with only modest positive predictive value.Conclusions: The S-MMSE and the IQCODE were individually poor at detecting CIND and dementia after a nonaphasic first-ever stroke. The combination was useful in detecting dementia but it does not replace the need for detailed neuropsychological tests. [ABSTRACT FROM AUTHOR]

Objective: To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study., Methods: The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10 -8 ., Results: We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10 -9 ). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21 , which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome ( p < 10 -5 ), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4 , TEK , and PTCH1 )., Conclusions: In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: No previous qualitative exploration of urinary incontinence (UI) or post-stroke urinary incontinence (PSUI) has been undertaken in an Australian population., Purpose: The purpose of this study is to explore the experiences of community-dwelling stroke survivors who were living with UI/PSUI and understand how context shaped those experiences., Methods: A pragmatic approach using thematic analysis was employed for this study., Findings: Four themes emerged from the data: "I've got to go": onset and daily experience of UI; "No one ever mentioned it": lack of advice and information from the health system; "You can't enjoy something if you've got to go the toilet": experience of occupational restrictions; and "It's just a matter of planning": management strategies., Implications: UI continued well beyond discharge and was shaped by limited advice, distress, and role loss. Occupational therapists are encouraged to engage in assessment, management, and treatment of UI, including the provision of education that promotes continence, attenuates negative experiences, and enhances community participation.

Background and Purpose: Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS., Methods: Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model., Results: Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons., Conclusions: Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Background: To date, EGF 61*A/G, TGF-β1 -509*T/C and TNF-α -308*A/G gene polymorphisms have been not been analysed in pancreatic carcinoma. This study investigated the frequency of these gene polymorphisms among patients with cancer of the pancreatic head., Patients and Methods: A total of 73 pancreatic head cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the University Hospital Mannheim. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analysed by PCR-RFLP., Results: The distribution of EGF 61*G/G homozygotes among pancreatic head cancer patients was more frequent than that in the control group (24.7% vs 11.1%, odds ratio (OR) = 2.618, 95% confidence interval (CI) = 1.195-5.738). In addition, the frequency of the G allele in the pancreatic head cancer patient group was also higher than that in the control group (45.9% vs. 33.3%, OR = 1.696, 95% CI = 1.110-2.592). No difference was found for the TGF-β1 -509 and TNF-α -308 genotypes among pancreatic head cancer patients and healthy controls., Conclusion: The frequencies of the EGF 61*G/G genotype and G allele are significantly increased among patients with pancreatic head cancer. TGF-β1-509*T/C and TNF-α -308*A/G gene polymorphisms are not related to this cancer entity.

Rationale: One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated. Aims POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score > or =8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score > or =8) and improved health-related quality of life in patients with a recent stroke., Design: A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups. STUDY OUTCOMES AND SAMPLE SIZE: For the primary end-point the POST trial will have 80% power to detect a relative risk of 0.4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up., Discussion: Evidence of efficacy will determine whether a multi-centre, international trial is warranted.

Introduction: Up to the present, EGF 61 A/G, TGF-beta1 -509 T/C, and VEGF 936 T/C gene polymorphisms have been analyzed in other cancer entities than colorectal cancer. We have now investigated the frequency of these gene polymorphisms among colorectal cancer patients., Material and Methods: A total of 157 colorectal cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the Universitätsklinikum Mannheim. All patients and healthy people are Caucasians. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: The distribution of EGF 61 G/G homozygotes among colorectal cancer patients was more frequent than that in the control group (33.1% versus 11.1%; Odds Ratio [OR]=3.962; 95% Confidence Interval [CI]=2.036-7.708). The frequency of the "G" allele in the colorectal cancer patient group was also higher than that in the control group (51.3% versus 33.3%; OR=2.105; 95% CI=1.482-2.988). No difference could be found for the TGF-beta1 and VEGF genotypes among colorectal cancer patients and healthy controls., Conclusions: The EGF 61 G/G genotype and the G allele are significantly related to colorectal cancer. The TGF-beta1 -509 T/C and VEGF 936 T/C gene polymorphisms are not related to colorectal cancer.

Background and Purpose: Incidence rates of stroke subtypes may be imprecise when samples are small. We aimed to determine the incidence of stroke subtypes in a large geographically defined population., Methods: Multiple overlapping sources were used to ascertain all strokes occurring in 22 postcodes (population of 306,631) of Melbourne, Australia, between 1997 and 1999. Stroke subtypes were defined by CT, MRI and autopsy. The Mantel-Haenszel age-adjusted rate ratio (MH RR) was used to compare incidence rates between men and women., Results: We identified 1,421 strokes among 1,337 residents, 1,035 (72.8%) being first-ever strokes. Incidence (number/100,000 population/year), adjusted to the European population 45-84 years, was 197 (95% confidence interval, CI, 169-224) for ischemic stroke (IS), 47 (95% CI 33-60) for intracerebral haemorrhage (ICH) and 19 (95% CI 10-27) for subarachnoid haemorrhage (SAH). Compared with women, men in this age group had a greater incidence of IS (MH RR 1.65, 95% CI 1.39-1.96, p < 0.0001) and ICH (MH RR 1.46, 95% CI 1.01-2.10, p = 0.0420), but lesser rates of SAH (MH RR 0.34, 95% CI 0.16-0.69, p = 0.0031)., Conclusions: In this population-based study, the incidence of IS and ICH was greater among men than women, while women had a greater incidence of SAH. More effort may need to be directed at modifying risk factors for IS and ICH in men., (2008 S. Karger AG, Basel)

Background: Handicap is rarely comprehensively examined after stroke. We examined handicap among 5-year stroke survivors from an 'ideal' stroke incidence study., Methods: Survivors were assessed with the London Handicap Scale [LHS, score range: 0 (greatest handicap) to 100 (least handicap)]. Multivariable regression was used to examine demographic, risk and stroke-related factors associated with handicap., Results: 351 of 441 (80%) survivors were assessed. Those assessed were more often Australian born than those not assessed (p < 0.05). The mean LHS score was 73 (SD = 21). The greatest handicap was present for physical independence and occupation/leisure items. Handicap was associated with older age, manual occupations, smoking, initial stroke severity, recurrent stroke and mood disorders., Conclusion: Reducing recurrent stroke, through better risk factor management, is likely to reduce handicap. The association between handicap and mood disorders, which are potentially modifiable, warrants further investigation., (Copyright (c) 2008 S. Karger AG, Basel.)

Objective: To elucidate the association of TNF-alpha-308G/A gene functional polymorphism with the development and progression of colorectal cancer., Methods: PCR-RFLP was employed to detect the TNF-alpha-308 G/A genotypes in 157 colorectal cancer patients and 117 healthy controls., Results: The frequency of TNF-alpha-308 genotype and allele were not significantly different between colorectal cancer patients and healthy controls (genotype chi(2)=1.054, P=0.591, allele chi(2)=0.404, P=0.525). The frequency of A/A genotype and A allele in III+IV stage (62 patients in total) were higher than those in I+II stages (85 patients in total) (A allele: 22.6% vs 12.9%, A/A genotype: 8.1% vs 1.2%), and the differences were significant (genotype P=0.048, OR=7.368, 95% CI=0.839-64.743, allele chi(2)=4.720, P=0.03, OR=1.962, 95% CI=1.061-3.628). The frequency of TNF-alpha-308 genotype were not significantly different among different colorectal cancer grades (chi(2)=3.009,P=0.591)., Conclusion: TNF-alpha-308G/A gene polymorphism is not associated with the development of colorectal cancer, but TNF-alpha-308 A/A genotype and A allele are related to the progression of colorectal cancer.

Background: Specific information about the nature of recurrent events that occur after each subtype of index stroke may be useful for refining preventive therapies. We aimed to determine whether stroke recurrence rates, the pattern of subtype recurrence, and prescription of secondary prevention agents differed according to initial stroke subtype., Methods: Multiple overlapping sources were used to recruit all first-ever stroke patients from a geographically defined region of Melbourne, Australia over a 3-year period from 1996 to 1999. Potential stroke recurrences (fatal and nonfatal) occurring within 2 years of the initial event were identified following patient interview and follow up of death records. Subjects were classified into the different Oxfordshire groups and the type of first-ever stroke was compared with recurrent stroke events., Results: One thousand, three hundred and sixteen first-ever strokes were registered during the 3-year period (mean age 74.4 years). A total of 103 first recurrent stroke events (fatal and nonfatal) occurred among those with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the 2-year follow-up period. The recurrent stroke subtype was different to the index stroke subtype in most (78%) patients. People with partial anterior circulation infarct had the greatest proportion of recurrences (13%), with a third of these being the more severe total anterior circulation infarct subgroup. The relative risk of ICH after an index lacunar infarct (LACI) compared with an index non-LACI was 4.06 (95% CI 1.10-14.97, P=0.038). Prescription of secondary prevention agents was greater at 2 years after stroke than at hospital discharge, and was similar between ischemic stroke subtypes., Conclusion: Approximately 9% of people with first-ever stroke suffered a recurrent event, despite many being prescribed secondary prevention agents. This has implications for the uptake of current preventive strategies and the development of new strategies. The possibility that ICH is greater among index LACI cases needs to be confirmed.

We present a male-to-female (MTF) transgender patient admitted with a pulmonary embolism. The patient had been treated with high-dose oestrogens since the age of 16. Following a prolonged period of hypotension, our patient sustained cerebral border zone infarcts. There was evidence of bilateral carotid stenosis on Doppler ultrasound. We discuss the treatment and vascular complications of gender dysphoria.

Post-stroke homonymous visual field (PSHVF) loss has functional and driving implications for patients. Automated, as opposed to confrontational, assessment of PSHVF loss has the potential to provide a more reliable indicator for field loss and thus ability to drive. Sixty-one consecutive stroke admissions were assessed at 9 months post-stroke. Driving status and the patient's awareness of any visual field loss was ascertained. Patients underwent formal perimetric visual field testing using a Humphrey Visual Field Analyser II. A separate, blinded, confrontational assessment of visual fields was made using the National Institutes of Health Stroke Scale (NIHSS) technique. Homonymous field defects were found in 10 (16%) patients, with 50% of these being hemianopia and 50% quadrantanopia. Right-sided field loss was more common (70%). No patients with PSHVF loss were aware of their loss, and only two were detected using NIHSS assessment. One patient was thought to have PSHVF loss on NIHSS assessment but this was not confirmed on perimetry. Of those with significant PSHVF loss at 9 months, 30% were driving. The prevalence of PSHVF loss is relatively high and is underestimated by confrontational testing. Stroke patients are often unaware of their field loss, with up to 5% driving with significantly affected visual fields at 9 months. Perimetric testing may be useful in decision-making regarding driving eligibility post-stroke.

Background: Early identification of mood disorder post-stroke (MDPS) or its determinants could improve stroke outcomes. However, the natural history, prevalence and determinants of MDPS within the first weeks post-stroke require further investigation., Methods: Consecutive hospitalised stroke survivors were assessed within 2-5 days of stroke, and at 1 and 3 months post-stroke. Baseline data included demographics, co-morbidities, stroke subtype, pre-stroke disability and cognition. At baseline, 1- and 3-month interviews physical impairment, disability, cognition and social support were assessed. MDPS was defined as a score of >8 on the depression subscale of the Hospital Anxiety Depression Scale. Factors independently associated with MDPS at each time-point were determined using regression analyses., Results: One hundred and twenty-five subjects were included. The prevalence of MDPS within 5 days and at 1 and 3 months post-stroke was 5%, 16% and 21% respectively. The independent determinants for MDPS at 1 month were disability, social support and change in impairment score between initial and 1-month assessments; and at 3 months were disability, social support and institutionalisation. Individuals moved in and out of the subset of depressed patients over time. MDPS was independently associated with mortality at 3 months post-stroke., Conclusion: Mood disorder post-stroke increases in prevalence over the initial weeks post-stroke despite an improvement in disability, and is associated with mortality. Patients with MDPS at 1 month were not necessarily affected at 3 months and vice versa, indicating the dynamic nature of MDPS in the early stages.

Objective: To investigate the association between VEGF gene 936 T/C polymorphism and colorectal cancer together with anastomotic leakage., Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the VEGF 936 T/C genotypes in colorectal cancer patients and healthy controls., Results: There was no significant difference in the frequency of VEGF 936 C/C genotype or C allele between colorectal cancer patients and healthy controls (P > 0.05). The C/C genotype or C allele in colorectal cancer patients with anastomotic leakage was less frequently found than in the group without anastomotic leakage (P < 0.05)., Conclusions: VEGF 936 C/C genotype or C allele is not related to the development of colorectal cancer, but they can reduce the risk of anastomotic leakage after surgery in colorectal cancer patients.

In tumor cells, high phosphorylation levels of receptor tyrosine kinases may occur in the absence of exogenous ligands due to autocrine signaling or enhanced tyrosine kinase activity. Here we show that the phosphorylation state of the endogenous epidermal growth factor receptor (EGFR) can be quantitatively imaged in tumor cells and tissues by detecting fluorescence resonance energy transfer between fluorophores conjugated to antibodies against the receptor and phosphotyrosine, respectively. Five different human colorectal cell lines were analyzed for activity and expression of EGFR. All cell lines exhibited basal EGFR phosphorylation under serum starvation conditions. Phosphorylation levels increased after stimulation with EGF or pervanadate, dependent on the level of basal EGFR phosphorylation in the respective cell lines. This basal activity correlated inversely with receptor expression. Using the acceptor photobleaching fluorescence resonance energy transfer imaging approach, a significantly higher phosphorylation state of EGFR was also found in resected human colorectal tumor samples as compared with adjacent healthy tissue. Imaging of EGFR phosphorylation may thus serve as a valuable tool to investigate the role of receptor tyrosine kinase activity in malignant cell growth.

Background: Although a number of acute stroke interventions are of proven efficacy, there is uncertainty about their community benefits. We aimed to assess this within a defined population., Methods: Eligibility for tissue plasminogen activator (tPA), aspirin, stroke unit management and neuroprotection were assessed among incident stroke cases within the community-based North East Melbourne Stroke Incidence Study., Results: Among 306,631 people, there were 645 incident strokes managed in hospital. When eligible patients were extrapolated to the Australian population, for every 1,000 cases, 46 (95% CI 17-69) could have been saved from death or dependency with stroke unit management, 6 (95% CI 1-11) by using aspirin, 11 (95% CI 5-17) or 10 (95% CI 3-16) by using tPA at 3 and 6 h, respectively., Conclusions: Although tPA is the most potent intervention, management in stroke units has the greatest population benefit and should be a priority.

Objectives: The cysteine proteases cathepsin B (CTSB) and L (CTSL) have been implicated in tumor spread and metastatic formation. In pancreatic adenocarcinoma, the role of these proteases is not very well defined. To find out which cell types produce CTSB and CTSL and to evaluate the prognostic impact of these proteases, 70 specimens from curatively resected patients with pancreatic adenocarcinoma were examined by in situ hybridization and immunohisto-chemistry., Methods: Seventy patients with ductal adenocarcinoma of the pancreas were studied after R0 resection with a follow-up of at least 3 years. CTSB and CTSL expression was performed immunohisto-chemically using polyclonal anti-CTSB and CTSL antibodies. To detect cell types involved in producing CTSB and CTSL as well as the intracellular localization of specific mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among CTSB and CTSL expression, clinicopathologic parameters, and clinical outcome were analyzed., Results: The immunoreactivity was 96% for CTSB and 90% for CTSL. Positive mRNA signals were obtained in the cytoplasm tumor cells, macrophages, and fibroblasts in 77% for CTSB and 81% for CTSL, respectively. Statistical analysis showed a significant correlation between CTSB/CTSL expression and tumor grading (P < 0.05) and between CTSB and lymphatic invasion (P = 0.05). Kaplan-Meier analyses revealed statistical significance for CTSB/CTSL expression with the survival after curative resection (P < 0.05). Both proteases are strong prognostic markers in multivariate analysis (P = 0.0001) beside UICC stage, nodal status, tumor size, and grading (P < 0.05). Furthermore, CTSB expression is an independent prognostic marker for cancer recurrence within 6 months after curative surgery in multivariate analysis (P = 0.0001)., Conclusions: CTSB and CTSL are strong and independent prognostic markers in resectable pancreatic adenocarcinoma rather than UICC stage, TNM classification, or tumor grading. Furthermore, CTSB is a predictor for early recurrence after curative resection. These data underline the significance of tumor-associated proteolysis for cancer invasion and metastasis and may lead to defining subgroups of patients with early recurrence and poor outcome.

Screening of patients at risk for hepatocellular carcinomas (HCC) and preventive virustatic therapy are the first steps in a multimodal treatment concept, because delayed detection leads to a poor prognosis with median survival of <10 months. Surgical resection of HCC is still the treatment of choice in patients with good residual liver function, however, recurrence-free 5-year survival after curative resection is low (33%). In patients with cirrhosis, only 25% of HCC are resectable, limited by low hepatic functional reserve. HCC in patients with non-cirrhotic livers are the domain of extended resections. In newer reports, transplantation in patients with cirrhosis is rated more positively when restricted to patients with solitary nodules <5 cm or up to 3 tumors <3 cm. A new option in HCC therapy are the local methods for tumor ablation, preferably radiofrequency ablation (RFA), especially in patients with limited liver function, non-resectable or multifocal tumors. A new horizon is opened combining these options and multimodal approaches with transarterial chemoembolisation (TACE). This trend to multimodal approaches promises a yet unknown improvement in the prognosis of patients with HCC. Controlled randomized studies comparing and validating the different methods and defining combined treatments according to liver function and tumor stage are eagerly awaited., (Copyright 2004 S. Karger GmbH, Freiburg)

Background: Vomiting, aspiration, and pneumonia are serious side effects in enteral feeding via percutaneous endoscopic gastrostomy (PEG), which often leads to hospitalization. To this day, it has not been proven whether pump-assisted (PA) or gravity-controlled application is the safer method for long-term feeding via PEG in bedridden patients., Methods: This study was conducted as a prospective, randomized crossover study. Fifty bedridden PEG patients were fed using the pump-assisted method (G1) and 50 patients were fed using the gravity-controlled feeding method (G2). After 6 weeks of observation (O1), the feeding methods in both groups were switched, followed by another 6 weeks of observation (O2). Daily recording was done using a standardized questionnaire. The glucose levels during O1 and O2 were determined on days 1, 21, and 42., Results: The patients in both groups were compatible in age, sex, and medical illness. By comparing G1 and G2, a significantly lower regurgitation rate (p < .0002), vomiting of feeding substrate (p < .009), aspiration (p < .01), and pneumonia (p < .02) was observed. The diarrhea rate in G2 was higher than in G1 (p < .007). The glucose profiles in G1 showed a significantly better development (p < .0007) than the ones in G2. After switching the application method in G2, the PA group (now G2) showed a significantly improved rate of regurgitation, vomiting, aspiration, and diarrhea and improved glucose profiles., Conclusion: Feeding via PA shows improved safety, which is documented in a lower rate of diarrhea, regurgitation, vomiting, and aspiration. PA also noted a more effective glucose metabolization, which results in better glucose levels. As a result of this prospective study, pump-assisted feeding is recommended for bedridden patients requiring long-term feeding via PEG.

Background/aims: To investigate postulated differences related to FGF-2 in liver morphology and expression of apoptosis-related factors after partial hepatectomy (PH)., Methods: Homogenous FGF-2-deficient mice (C57BL/6J) with their FGF-2-(+/+) littermates (control) were used to examine the structure of regenerating livers after PH with light and electron microscopy. The regenerative response and BrDu incorporation were monitored. The expression of BclX-l, Bax, Fas, TNF-alpha, and Caspase-3 were measured by reverse transcription PCR (RT-PCR) and Northern blot analysis., Results: In the FGF-2-(-/-) group, hepatocytes and endothelial cells contain mitochondria with atypical cristae and fragmented endoplasmic reticulum structures compared to control. Sinusoids show irregular basal laminae. These changes are in accordance with a differential expression of apoptosis-related factors: FasL was expressed throughout the entire observation span (days 0 to 10 post-PH). Following PH, tumor necrosis factor alpha (TNFalpha)-mRNA levels were higher in FGF-2-(+/+) animals, while Fas as well as Bax and BclXl were overexpressed in FGF-2-(-/-) mice. Caspase-3-mRNA was similarly expressed in both groups, but Caspase-3 activity was elevated for 4 days in FGF-2-(-/-) mice., Conclusion: Despite morphologic differences, differences in the time schedule of DNA synthesis and differences in apoptotic response, the dynamics of liver regeneration in FGF-2-(-/-) mice were not impaired., (Copyright 2004 S. Karger AG, Basel)

The level of TNFalpha expression is increased after partial hepatectomy, and experimental evidence exists that TNFalpha plays a key role in liver regeneration. Contradictory results are reported about the influence of TNFalpha on tumor growth: on the one hand, stimulation of tumor growth in various animal models and, on the other hand, intraperitoneally administered TNFalpha leads to reduced metastasis formation. TNFalpha may be one responsible factor for increased metastasis formation after surgical trauma. The objective of our study was to clarify the influence of TNFalpha on the formation of liver metastases in a syngenic mouse model in vivo. We used a novel marker system, EGFP transfected C26 tumor cells for in vivo observation of metastasis formation by intravital microscopy. We analyzed the effect of intraperitoneal TNFalpha-injection on tumor cell adhesion, extravasation and tumor development. The expression of ICAM-1, VCAM-1 and E-Selectin was measured by Western blot and immunohistochemical staining. Tumor load was assessed by determining EGFP in Western blots. GdCl(3) was employed 24 and 48 hr before tumor cell injection to selectively deplete the liver of functioning Kupffer cells. We observed significantly more extravasated tumor cells in the TNFalpha-pre-treated animals at early time points with increased expression of adhesion molecules. Measurement of the EGFP levels showed fewer liver metastases in the TNFalpha-pretreated animals at day 8. After GdCl(3) pretreatment even lower levels of EGFP, i.e., fewer metastases and also lower expression levels of ICAM-1, VCAM-1 and E-Selectin could be observed. TNFalpha, acts in a bidirectional manner: whereas TNFalpha facilitates tumor cell adhesion and extravasation of C26 tumor cells by inducing the expression of adhesion molecules, at later time points, TNFalpha seems to hinder the formation of liver metastases., (Copyright 2003 Wiley-Liss, Inc.)

Background: Vomiting, aspiration, flatulence, and diarrhea are well-known negative side effects of enteral nutrition through percutaneous endoscopic gastrostomy (PEG). However, it is not yet clarified if pump-assisted (PA) or gravity-controlled (GC) application is the more comfortable and safe choice for long-term nutrition through PEG., Methods: This was a prospective, randomized, crossover study. Fifty long-term PEG patients were fed by PA nutrition (G1) and 50 patients were fed by GC nutrition (G2). Six weeks of observation (O1) was followed by a switch of method of nutritional application in both groups and an additional 6 weeks of observation (O2). Daily determination of comfort and safety was done with a standardized questionnaire. Evaluation of blood glucose levels on days 1, 21, and 42 during O1 and O2., Results: The patients in both groups had the same medical conditions and were of the same age and sex. Far less flatulence (p < .0006) and epigastric fullness (p < .0003) was discovered in G1 during O1. Also, significantly less regurgitation (p < .0002) and vomiting of feeding diet (p < .0001) in G1 versus G2 could be observed. The rate of diarrhea (p < .0003) in G2 was higher than in G1. The daily profile of blood glucose was significantly better (p < .0008) in G1 than in G2. After the nutritional application was changed in O2, the PA group (G2) again showed a significantly better rate of flatulence, epigastric fullness, regurgitation, vomiting, diarrhea, and daily profile of blood glucose. Ninety-six percent of the patients in G2 preferred further nutrition by PA after finishing this study. All patients in G1 continued their accustomed nutrition by PA., Conclusion: Nutrition through PA showed not only a higher comfort rate but also increased safety, which was expressed through a low rate of regurgitation and vomiting. PA presented better glucose metabolization manifested in improved blood glucose levels. As a result of this prospective study, PA is preferable to GC and preferred by patients with long-term PEG nutrition.

The prognosis of patients who undergo resection for pancreatic ductal adenocarcinoma with curative intention is generally poor unless they have early-stage disease. Based on our 25-year experience, the results of 194 patients after a standardized Kausch-Whipple resection for adenocarcinoma of the pancreatic head were analyzed and the prognostic factors were evaluated. Between 1972 and 1998 a total of 221 patients were diagnosed for ductal adenocarcinoma of the pancreatic head, and 194 of them subsequently underwent a standardized Kausch-Whipple resection. Long-term results and prognostic factors were examined by multivariate and univariate analyses. The overall postoperative mortality was 3.09%, and the morbidity was 29.9%. By multivariate analysis only curative resection (R0) was significantly related to a favorable prognosis ( p < 0.0001). Furthermore, in case of a curative resection, the presence of lymph node metastases showed prognostic significance in the multivariate analysis ( p = 0.005). Cumulative survival analysis revealed a 5-year survival rate of 25.4%, a 7-year survival rate of 12.3%, and a 10-year survival rate of 8.2% for patients who underwent curative resection (R0) for adenocarcinoma of the pancreatic head. We demonstrated that the R0 status is the only independent prognostic factor after surgery for adenocarcinoma of the pancreatic head. In the case of a curative resection, the presence of lymph node metastases is of prognostic relevance. In view of considerable surgical morbidity and mortality, resection for cancer of the pancreatic head is the only option if the lesion is resectable. We concluded that surgical treatment is "as good as it gets," as extended techniques have not proved to produce better results.

Many animal models for metastatic colorectal cancer represent clinical manifestations just inaccurately. We introduce a novel mouse model for metastastatic colorectal cancer. In order to remain close to the clinical disease a syngenic murine colon carcinoma cell line (colon 26 cells) was transfected with enhanced green fluorescent protein (EGFP). The transfected cells maintain the highly malignant attributes of the wild-type cells. Following injection into the portal circulation of Balb/c-mice, liver metastases occur in the same time span. Using the fluorescent attributes of the transfected cells, an approximation of the tumor load in liver tissue can be achieved by fluorescence activated cell sorting (FACS) and fluoroscan analysis. Tumor cell load in liver tissue can be accurately measured by Northern blot and Western blot analysis of liver tissue containing EGFP-transfected colon cancer metastases (1250 cells/mg liver tissue and 1000 cells/mg liver tissue) respectively. Confocal microscopy and intravital microscopy confirmed the growth of tumor metastases, originating from the intravascular compartments. The presented animal model using EGFP-transfected colon 26 cells allows the detecting of tumor growth in vivo and post mortem, as well as an accurate quantification of the tumor load in the liver tissue.

Cure for ductal adenocarcinoma of the pancreas is restricted to resectable tumors, but survival after surgery is still poor. Despite apparently curative resection, these cancers rapidly recur. Thus, the present pathologic examination should be enriched by sensitive methods to detect minimal residual disease. In a prospective setting we studied the frequency of minimal residual disease after curative resection by routine histopathology, immunohistology, and polymerase chain reaction (PCR) for mutated K-ras. Furthermore, the prognostic implication of detecting of MRD was determined. Prospectively, tumor tissue and corresponding paraaortic lymph nodes were obtained from 78 patients, who underwent surgery for pancreatic head tumors between 1999 and 2001. Sixty-nine of 78 cases were diagnosed for ductal adenocarcinoma (study group), whereas nine cases were diagnosed for benign pancreatic tumors (control group). Paraaortic lymph nodes were examined in step sections by routine histopathology (hematoxylin and eosin) and immunohistology using a pan-cytokeratin antibody. DNA of the primary tumor and corresponding paraaortic lymph nodes were analyzed by PCR-based assays with respect to mutated K-ras in codon 12. The recurrence-free survival and overall survival were correlated with the results of the latter methods. In 3 of 69 patients tumor cells were detected in paraaortic lymph nodes by routine histopathology and in 5 of 69 patients by immunohistology. K-ras mutations were detected in 42 of 69 ductal adenocarcinomas (61%), whereas 12 (17%) were positive in paraaortic lymph nodes. All of the latter patients had recurrence after surgery and a significant poorer survival than those without mutated K-ras. Furthermore, paraaortic lymph nodes diagnosed for K-ras mutation were independent prognostic markers in multivariate analysis. In the control group K-ras mutations were detected in one adenoma of Vater's papilla but not in paraaortic lymph nodes. Tumor cell DNA can be detected more sensitively by the described PCR method than with hematoxylin and eosin or immunohistologic staining, leading to a higher sensitivity for detection of micrometastases. The described PCR method clearly determines subgroups of patients after curative resection with early recurrence and poor survival and could therefore enrich the pathologic examination.

Although precipitation of seizures by exercise has been described, the reproducible induction of temporal lobe seizures by exercise is unusual. The authors report two patients with left temporal lobe seizures induced by exercise. In one patient the family history suggested autosomal-dominant inheritance. Prolonged hyperventilation, simple movements, and visualization of a competitive game did not produce epileptiform discharges on the interictal EEG.

Introduction and Aims: Only curative resection for pancreatic adenocarcinoma is related to a favorable prognosis, but the overall survival after surgery still remains poor, and early recurrence is frequently observed. Because recurrence is the limiting factor and the main cause of death after curative resection, the identification of markers that predict early postoperative recurrence is of paramount importance. Angiogenesis is essential for tumor growth and metastases; therefore, we set out to clarify whether vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) correlate with early recurrence and poor prognosis after curative resection. A second goal was to characterize the VEGF-producing cells and the subcellular distribution., Methodology: Seventy patients with ductal adenocarcinoma of the pancreas were studied after curative resection with a follow-up of at least 2 years. The MVD quantification was performed immunohistochemically with use of a monoclonal antibody to CD34. The VEGF expression was studied with use of polyclonal antibody. To detect the intracellular localization of specific VEGF mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among VEGF expression and MVD, clinicopathologic parameters, and clinical outcome were then statistically analyzed., Results: The VEGF immunoreactivity was 88.6%, and positive mRNA signals were obtained in the cytoplasm of carcinoma and endothelial cells in 81.4%. Furthermore, we observed tumor-associated macrophages close to infiltrating carcinoma cells. All endothelial cells showed positive immunoreactivity to the anti-CD34 antibody, and a median distribution of 85 vessels/x200 field was observed. A significant correlation (p < 0.05) was found between the MVD and the International Union Against Cancer (UICC) stage. Statistical analysis showed a significant correlation between VEGF expression and the height of MVD (p < 0.05). Kaplan-Meier analyses revealed that VEGF expression and MVD had a statistically significant correlation with survival after curative resection (p < 0.05). Furthermore, multivariate analysis indicated that VEGF expression is an independent prognostic marker for cancer recurrence within 8 months after curative surgery (p = 0.003)., Conclusion: In pancreatic adenocarcinoma, the VEGF expression and the height of MVD are closely correlated, and both-rather than UICC stage and TNM classification (tumor size and nodal involvement)-are markers of prognostic relevance after curative resection. Furthermore, VEGF is a predictor of early recurrence after curative resection. The current study indicates that VEGF may promote the distribution of metastases, leading to early cancer recurrence and poor outcome.

Objectives: To determine the prevalence of stroke risk factors in a general practice population and to identify pharmacotherapies currently used in management of stroke risk factors., Design: Multicentre, observational study by 321 randomly selected general practitioners who each collected data on 50 consecutive patients attending their surgery., Patients and Setting: 16 148 patients aged 30 years or older attending general practices across Australia during 2000., Outcome Measures: Prevalence of hypertension, current smoking, diabetes, hypercholesterolaemia, atrial fibrillation, recent history of stroke or TIA; extent of pharmacotherapy use in risk-factor management., Results: 70% of patients had one or more risk factors and 34% had two or more. Hypertension was the risk factor with greatest prevalence (44%), followed by hypercholesterolaemia (43%) and current smoking (17%). The prevalence of risk factors generally increased with age, except for current smoking, where a decrease with age was seen. The most common pharmacotherapies were cardiovascular agents, followed by antiplatelet agents. Two-thirds of patients with hypertension were taking cardiovascular drugs, most commonly angiotensin-converting enzyme inhibitors., Conclusions: Stroke risk factors are highly prevalent in general practice patients and GPs are ideally placed for opportunistic case-finding. There is considerable scope for improving management of stroke risk factors. The Avoid Stroke as Soon as Possible (ASAP) general practice stroke audit provides a baseline against which progress in risk-factor management can be measured.

Objective: To find out whether there is any benefit from venous resection during pancreaticoduodenectomy for ductal pancreatic adenocarcinoma., Design: Retrospective study., Setting: University Hospital Mannheim/Heidelberg, Germany., Interventions: 271 patients had resections for ductal adenocarcinoma of the pancreatic head between 1980 and 2001. The outcome of patients who did (n = 68) and who did not (n = 203) have simultaneous resection of major veins (portal vein and/or superior mesenteric vein) were compared., Main Outcome Measurement: 5 year survival., Results: The groups differed significantly regarding stage, perineural infiltration, lymphangiosis carcinomatosa, operating time, blood loss, and blood transfusion. However, there was no difference in perioperative morbidity (27% and 22%), mortality (4% and 3%), and long-term survival (at 5 years 23% and 24%). Subgroup analysis of patients with margins free of tumour (R0 resections) showed that those patients who had venous resections in whom histological examination did not show infiltration of tumour had the most favourable outcome., Conclusion: There is no reason to exclude patients with suspected venous infiltration from radical pancreaticoduodenectomy including venous resection.

Objective: To find out if resections of cancers of the head of pancreatic are justified in patients over the age of 70 years., Design: Retrospective study., Setting: University hospital, Germany., Subjects: 519 patients with cancers of the pancreatic head, 93 (18%) of whom were aged 70 or over., Main Outcome Measures: Comparison of outcomes between those aged 70 or over, and those aged less than 70., Results: There were 247 ductal adenocarcinomas, 134 carcinomas of the papilla of Vater, 79 carcinomas of the distal common bile duct, and 59 miscellaneous tumours. Of all variables compared (age, sex, symptoms, operations, clinical and pathological stage. morbidity, mortality, and long-term survival) the only significant difference between the groups was that leaks from the pancreaticojejunostomy occured more often in the older age group (p = 0.02). However, this did not influence overall morbidity or mortality., Conclusion: Patients' age is not a limiting factor in attempts at curative resection of cancers of the head of pancreas. If the tumour is resectable and patient is motivated and well enough, resection is indicated whatever the age.