| 11. |
- Andréasson, Håkan, et al.
(författare)
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Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
- 2012
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 38:10, s. 962-968
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.PATIENTS AND METHODS:Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.RESULTS:One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).CONCLUSIONS:CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.
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| 12. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 13. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 14. |
- Berglund, Åke, et al.
(författare)
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An explorative randomised phase II study of sequential chemotherapy in advanced upper gastrointestinal cancer
- 2010
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 27:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric (GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m2 docetaxel or 180 mg/m2 irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were reasonably well tolerated. Grade 3–4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and appears active in advanced UGIA.
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| 15. |
- Bidleman, Terry F., et al.
(författare)
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Air-water exchange of brominated anisoles in the northern baltic sea
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:11, s. 6124-6132
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Tidskriftsartikel (refereegranskat)abstract
- Bromophenols produced by marine algae undergo O-methylation to form bromoanisoles (BAs), which are exchanged between water and air. BAs were determined in surface water of the northern Baltic Sea (Gulf of Bothnia, consisting of Bothnian Bay and Bothnian Sea) during 2011-2013 and on a transect of the entire Baltic in September 2013. The abundance decreased in the following order: 2,4,6-tribromoanisole (2,4,6-TBA) > 2,4-dibromoanisole (2,4-DBA) ≫ 2,6-dibromoanisole (2,6-DBA). Concentrations of 2,4-DBA and 2,4,6-TBA in September were higher in the southern than in the northern Baltic and correlated well with the higher salinity in the south. This suggests south-to-north advection and dilution with fresh riverine water enroute, and/or lower production in the north. The abundance in air over the northern Baltic also decreased in the following order: 2,4,6-TBA > 2,4-DBA. However, 2,6-DBA was estimated as a lower limit due to breakthrough from polyurethane foam traps used for sampling. Water/air fugacity ratios ranged from 3.4 to 7.6 for 2,4-DBA and from 18 to 94 for 2,4,6-TBA, indicating net volatilization. Flux estimates using the two-film model suggested that volatilization removes 980-1360 kg of total BAs from Bothnian Bay (38000 km(2)) between May and September. The release of bromine from outgassing of BAs could be up to 4-6% of bromine fluxes from previously reported volatilization of bromomethanes and bromochloromethanes.
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| 16. |
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| 17. |
- Byström, P., et al.
(författare)
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An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 24:6, s. 1645-1652
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Tidskriftsartikel (refereegranskat)abstract
- The value of early tumour marker changes during palliative chemotherapy in patients with upper gastrointestinal adenocarcinoma (UGIA) is unclear. Seventy-three patients with advanced UGIA were randomised to receive 45 mg/m2 docetaxel or 180 mg/m2 irinotecan with 5-FU/leucovorin. After every 2nd course the patients were crossed over to the other regimen. Serum was sampled before start of chemotherapy and every 2nd week during 8 weeks for CEA, TPA, TPS, CA72-4, CA19-9 and CA242 measurements. Eighteen patients (25%) had partial response (PR) and 21 patients had stable disease for at least 4 months (SD4). All baseline marker levels, except CA72-4, correlated with time to progression and survival. Patients with normal levels, except CA72-4, also had more clinical responses (PR+SD4) than patients with elevated values. Tumour marker changes early during treatment provided modest predictive information for tumour response and survival. A model combining baseline level, the change and the interaction between them gave the best prediction of outcome, however, insignificantly better than baseline level for all markers except CA242. Baseline tumour marker levels provide prognostic information for patients with UGIA on palliative chemotherapy. Early changes generally failed to provide accurate information for tumour response and survival.
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| 18. |
- Byström, Per, et al.
(författare)
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Evaluation of predictive markers for patients with advanced colorectal cancer
- 2012
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:7, s. 849-859
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Tidskriftsartikel (refereegranskat)abstract
- Background.To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.Material and methods.One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.Results.A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.Conclusions.Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.
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| 19. |
- Cancelliere, Carol, et al.
(författare)
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Protocol for a systematic review of prognosis after mild traumatic brain injury : an update of the WHO Collaborating Centre Task Force findings
- 2012
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Ingår i: Systematic Reviews. - : Springer Science and Business Media LLC. - 2046-4053. ; :1, s. 17-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild traumatic brain injury (MTBI) is a major public-health concern and represents 70-90% of all treated traumatic brain injuries. The last best-evidence synthesis, conducted by the WHO Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation in 2002, found few quality studies on prognosis. The objective of this review is to update these findings. Specifically, we aim to describe the course, identify modifiable prognostic factors, determine long-term sequelae, and identify effects of interventions for MTBI. Finally, we will identify gaps in the literature, and make recommendations for future research.Methods: The databases MEDLINE, PsychINFO, Embase, CINAHL and SPORTDiscus were systematically searched (2001 to date). The search terms included 'traumatic brain injury', 'craniocerebral trauma', 'prognosis', and 'recovery of function'. Reference lists of eligible papers were also searched. Studies were screened according to pre-defined inclusion and exclusion criteria. Inclusion criteria included original, published peer-reviewed research reports in English, French, Swedish, Norwegian, Danish and Spanish, and human participants of all ages with an accepted definition of MTBI. Exclusion criteria included publication types other than systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case-control studies; as well as cadaveric, biomechanical, and laboratory studies. All eligible papers were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers performed independent, in-depth reviews of each eligible study, and a third reviewer was consulted for disagreements. Data from accepted papers were extracted into evidence tables, and the evidence was synthesized according to the modified SIGN criteria.Conclusion: The results of this study form the basis for a better understanding of recovery after MTBI, and will allow development of prediction tools and recommendation of interventions, as well as informing health policy and setting a future research agenda.
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| 20. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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