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| 2. |
- Björnsson, Bergthor, et al.
(författare)
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Associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases - Intermediate oncological results
- 2016
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Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 42:4, s. 531-537
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two-stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. Material and methods: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. Results: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 nun (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. Conclusion: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH. (C) 2016 Elsevier Ltd. All rights reserved.
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| 4. |
- Björnsson, Bergthor, et al.
(författare)
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Associating Liver Partition and Portal Vein Ligation for Primary Hepatobiliary Malignancies and Non-Colorectal Liver Metastases
- 2016
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Ingår i: Scandinavian Journal of Surgery. - : SAGE PUBLICATIONS LTD. - 1457-4969 .- 1799-7267. ; 105:3, s. 158-162
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Associating liver partition and portal vein ligation for staged hepatectomy may increase the possibility of radical resection in the case of liver malignancy. Concerns have been raised about the high morbidity and mortality associated with the procedure, particularly when applied for diagnoses other than colorectal liver metastases. The aim of this study was to analyze the initial experience with associating liver partition and portal vein ligation for staged hepatectomy in cases of non-colorectal liver metastases and primary hepatobiliary malignancies in Scandinavia. Materials and Methods: A retrospective analysis of all associating liver partition and portal vein ligation for staged hepatectomy procedures performed at two Swedish university hospitals for non-colorectal liver metastases and primary hepatobiliary malignancies was performed. The primary focus was on the safety of the procedure. Results and Conclusion: Ten patients were included: four had hepatocellular cancer, three had intrahepatic cholangiocarcinoma, one had a Klatskin tumor, one had ocular melanoma metastasis, and one had a metastasis from a Wilms tumor. All patients completed both operations, and the highest grade of complication (according to the Clavien-Dindo classification) was 3A, which was observed in one patient. No 90-day mortality was observed. Radical resection (R0) was achieved in nine patients, while the resection was R2 in one patient. The low morbidity and mortality observed in this cohort compared with those of earlier reports on associating liver partition and portal vein ligation for staged hepatectomy for diagnoses other than colorectal liver metastases may be related to the selection of patients with limited comorbidity. In addition, procedures other than associating liver partition and portal vein ligation for staged hepatectomy had been avoided in most of the patients. In conclusion, associating liver partition and portal vein ligation for staged hepatectomy can be applied to primary hepatobiliary malignancies and non-colorectal liver metastases with acceptable rates of morbidity and mortality.
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| 5. |
- Cockerill, Christopher Alan, 1994-, et al.
(författare)
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Genomic Consequences of Fragmentation in the Endangered Fennoscandian Arctic Fox (Vulpes lagopus)
- 2022
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Accelerating climate change is causing severe habitat fragmentation in the Arctic, threatening the persistence of many cold-adapted species. The Scandinavian arctic fox (Vulpes lagopus) is highly fragmented, with a once continuous, circumpolar distribution, it struggled to recover from a demographic bottleneck in the late 19th century. The future persistence of the entire Scandinavian population is highly dependent on the northernmost Fennoscandian subpopulations (Scandinavia and the Kola Peninsula), to provide a link to the viable Siberian population. By analyzing 43 arctic fox genomes, we quantified genomic variation and inbreeding in these populations. Signatures of genome erosion increased from Siberia to northern Sweden indicating a stepping-stone model of connectivity. In northern Fennoscandia, runs of homozygosity (ROH) were on average ~1.47-fold longer than ROH found in Siberia, stretching almost entire scaffolds. Moreover, consistent with recent inbreeding, northern Fennoscandia harbored more homozygous deleterious mutations, whereas Siberia had more in heterozygous state. This study underlines the value of documenting genome erosion following population fragmentation to identify areas requiring conservation priority. With the increasing fragmentation and isolation of Arctic habitats due to global warming, understanding the genomic and demographic consequences is vital for maintaining evolutionary potential and preventing local extinctions.
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| 10. |
- Hasselgren, K., et al.
(författare)
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ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
- 2021
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Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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| 11. |
- Hasselgren, Kristina, 1976-, et al.
(författare)
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Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO
- 2019
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Ingår i: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 23:3, s. 556-562
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPortal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.MethodsPatients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.ResultsForty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (4), compared to 1.5 (+/- 2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (+/- 4) the first week, compared to 4.3 (+/- 2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (+/- 2), respectively (+/- 0.1) (p=0.017).Discussion p id=Par4 The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.
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| 14. |
- Hasselgren, Malin, et al.
(författare)
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Genetic rescue in an inbred Arctic fox (Vulpes lagopus) population
- 2018
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 285:1875
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Tidskriftsartikel (refereegranskat)abstract
- Isolation of small populations can reduce fitness through inbreeding depression and impede population growth. Outcrossing with only a few unrelated individuals can increase demographic and genetic viability substantially, but few studies have documented such genetic rescue in natural mammal populations. We investigate the effects of immigration in a subpopulation of the endangered Scandinavian arctic fox (Vulpes lagopus), founded by six individuals and isolated for 9 years at an extremely small population size. Based on a long-term pedigree (105 litters, 543 individuals) combined with individual fitness traits, we found evidence for genetic rescue. Natural immigration and gene flow of three outbred males in 2010 resulted in a reduction in population average inbreeding coefficient (f), from 0.14 to 0.08 within 5 years. Genetic rescue was further supported by 1.9 times higher juvenile survival and 1.3 times higher breeding success in immigrant first-generation offspring compared with inbred offspring. Five years after immigration, the population had more than doubled in size and allelic richness increased by 41%. This is one of few studies that has documented genetic rescue in a natural mammal population suffering from inbreeding depression and contributes to a growing body of data demonstrating the vital connection between genetics and individual fitness.
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| 15. |
- Nordén, T, et al.
(författare)
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Mammographic screening for breast cancer : What cancers do we find?
- 1997
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 33:4, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme, and 149 primary breast cancers were diagnosed clinically. Lymph node involvement was evaluated in univariate and multivariate logistic regression models correcting for tumour size, histological grade, steroid receptor status and DNA-ploidy. Patients with screen-detected cancers had a low relative risk of having lymph node metastases (univariate, OR = 0.31; 95% confidence interval = 0.19-0.52). In the multivariate logistic regression model, the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more pronounced for women younger than 50 years of age compared to older women. The risk for screen-detected cases of having lymph node metastases at diagnosis was statistically significantly lower than for clinically-detected cases. The marked reduction, even when correcting for tumour size, makes it less likely that factors such as detection of clinically innocent tumours, length bias sampling or clinical symptoms related to axillary metastases can explain the whole difference. The results indicate at least part of the effect may be explained by tumour progression in the late preclinical detectable phase.
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| 16. |
- Norden, T, et al.
(författare)
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Mammographic screening for breast cancer. What cancers do we find?
- 1997
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Ingår i: EUROPEAN JOURNAL OF CANCER. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0959-8049. ; 33:4, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme
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| 19. |
- Sundh, Josefin, 1972-, et al.
(författare)
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Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
- 2020
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
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| 20. |
- Tietgen, Lukas, et al.
(författare)
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Fur colour in the Arctic fox : genetic architecture and consequences for fitness
- 2021
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 288:1959
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies provide good opportunities for studying the genetic basis of adaptive traits in wild populations. Yet, previous studies often failed to identify major effect genes. In this study, we used high-density single nucleotide polymorphism and individual fitness data from a wild non-model species. Using a whole-genome approach, we identified the MC1R gene as the sole causal gene underlying Arctic fox Vulpes lagopus fur colour. Further, we showed the adaptive importance of fur colour genotypes through measures of fitness that link ecological and evolutionary processes. We found a tendency for blue foxes that are heterozygous at the fur colour locus to have higher fitness than homozygous white foxes. The effect of genotype on fitness was independent of winter duration but varied with prey availability, with the strongest effect in years of increasing rodent populations. MC1R is located in a genomic region with high gene density, and we discuss the potential for indirect selection through linkage and pleiotropy. Our study shows that whole-genome analyses can be successfully applied to wild species and identify major effect genes underlying adaptive traits. Furthermore, we show how this approach can be used to identify knowledge gaps in our understanding of interactions between ecology and evolution.
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| 23. |
- Zetterström, Caroline E., 1982-, et al.
(författare)
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The Resveratrol Tetramer (-)-Hopeaphenol Inhibits Type III Secretion in the Gram-Negative Pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa
- 2013
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)- Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.
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