| 1. |
- Hansson, Josefin, et al.
(författare)
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The risk of graft loss 5 years after kidney transplantation is increased if cold ischemia time exceeds 14 hours
- 2018
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063. ; 32:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The state of the evidence is unclear regarding the impact of cold ischemia time (CIT) on the outcome of kidney transplantation. The aim of this study was to investigate the effect of CIT on the short- and long-term function of kidneys transplanted at the Sahlgrenska University Hospital in 2007-2009 from donors after brain death (DBDs). Methods: This study was designed as a retrospective analysis of data from local and national transplantation registers. The study endpoints were as follows: delayed graft function (DGF), primary nonfunction (PNF), biopsy-proven acute rejection (BPAR), serum creatinine (S-creatinine) level at discharge, days of hospitalization after transplantation, and graft survival at 5 years post-transplantation. Adjusted regression analyses were used to determine causal relationships with CIT. A further aim was to estimate a threshold for CIT by analyzing event rates and coordinates of the receiver-operated characteristic (ROC) curve. Results: There was a causal relationship between CIT as a continuous variable and the following endpoints: graft survival at 5 years post-transplantation, though this was not significant (hazard ratio (HR) 1.07, P = 0.057), DGF (odds ratio (OR) 1.09, P = 0.03) and S-creatinine (P = 0.003). In our material, the risk for impaired outcome was higher with longer CIT. We were therefore able to estimate a threshold value for CIT, set to 14 hours for both graft survival at 5 years post-transplantation and DGF. This was proved with significance by analyzing both event rates and the coordinates of the ROC curve. The risk of graft loss increased, with HR 2.3 (P = 0.023), when comparing a CIT cutoff of >= 14 hours with CIT < 14 hours. Delayed graft function increased, with an OR of 2.6 (P = 0.001). Conclusion: Our study confirms that, in this patient material, longer CIT was associated with increased risk for both impaired graft survival and incidence of DGF. We estimated a threshold for CIT of 14 hours.
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| 2. |
- Ben-Shabat, Ilan, et al.
(författare)
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Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.
- 2015
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Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :95
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Tidskriftsartikel (refereegranskat)abstract
- Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
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| 3. |
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| 4. |
- Johansson, Junko, 1989, et al.
(författare)
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Isolated Limb Perfusion With Melphalan Triggers Immune Activation in Melanoma Patients
- 2018
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Hyperthermic isolated limb perfusion with melphalan (M-ILP) is a treatment option for melanoma patients with metastases confined to the limbs. This study aimed at defining the role of cellular immunity for the clinical response to M-ILP in melanoma patients. It was observed that patients with enhanced cytotoxic CD8(+) T cell reactivity to common antigens (HCMV/EBV/influenza virus) prior to M-ILP were more likely to achieve a complete disappearance of macroscopic tumors (complete response). Following M-ILP treatment, the proportions of CD16(+) intermediate and non-classical monocytes in peripheral blood were significantly enhanced along with induction of HLA-DR on CD4(+) and CD8(+) T cells. For further studies of the mechanism behind melphalan-induced immune activation an in vitro model, aiming at mimicking the clinical M-ILP protocol, was established, where PBMCs were co-cultured with melanoma cells, which had been pre-exposed to melphalan under mild hyperthermia. Upon exposure to melphalan, melanoma cells showed increased expression of immune-related markers including MHC class I and Hsp70. Moreover, when the melphalan-treated melanoma cells were co-cultured with PBMCs, this triggered an increased proportion of CD33(+)CD14(+)CD16(++) non-classical monocytes among the PBMCs. Furthermore, the melphalan-treated melanoma cells stimulated the expansion of CD8(+) T cells in the co-cultured PBMCs. These cells produced enhanced levels of IFN-gamma and granzyme B and were capable of killing melanoma cells. To further verify an immunogenic role of melphalan, mice were vaccinated with melphalan-exposed murine melanoma cells. When challenged with live melanoma cells, vaccinated mice showed reduced tumor growth and enhanced infiltration of tumor-specific T cells into tumors. We conclude that melphalan-exposed melanoma cells trigger expansion of CD16(+) monocytes and activate cytotoxic T cells and that these events may contribute to the antitumoral efficacy of M-ILP.
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| 5. |
- Lindnér, Per, 1956, et al.
(författare)
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Gallbladder cancer - no improvement in survival over time in a Swedish population
- 2018
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 57:11, s. 1482-1489
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gallbladder cancer (GBC) has an extremely poor outcome. The aim of this study was to examine trends in GBC incidence, treatment and overall survival in a complete population of affected persons in a well-defined region in Sweden in 2000-2014. Material and methods: Altogether 546 individuals with GBC were identified at Sweden's Regional Cancer Centre West. Subjects were grouped into three 5-year periods (Period A: 2000-2004, Period B: 2005-2009 and Period C: 2010-2014) and the survival, diagnosis, staging, grading and treatment for each period were investigated. Patients dead at date of diagnosis (n = 39) and patients with not invasive cancer (n = 25) were not included in the analysis. Results: The incidence was unchanged over the study period. The survival curves for the time periods were not significantly separated. Median survival was 4.7 months in Period A, 4.8 months in Period B and 6.1 months in Period C. Stage migration to more M1 in Periods B and C occurred and survival was improved for these cohorts. More individuals were diagnosed using only diagnostic imaging (p = .02). There were 177 curatively aiming operative procedures carried out on 482 persons (37%). The survival after surgery for the three periods improved over time (p = .02). Individuals who underwent a liver bed resection after a cholecystectomy had better survival than individuals who had cholecystectomy combined with liver resection. More persons were treated with chemotherapy, but no significant impact was found on survival in the total GBC population. Conclusions: Although there were signs of improved diagnosis of GBC, the survival rate did not improve over time. There was a significant stage migration to more M1 in Periods B and C. Therapeutics able to downsize a cancer and increase the effectiveness of surgery with curative intent are warranted.
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| 6. |
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| 7. |
- Lindnér, Per, 1956, et al.
(författare)
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The impact of changed strategies for patients with cholangiocarcinoma in this millenium.
- 2015
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Ingår i: HPB surgery : a world journal of hepatic, pancreatic and biliary surgery. - : Hindawi Limited. - 0894-8569. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- Background. Cholangiocarcinoma is a cancer with a poor prognosis. In this millennium there are new diagnostic and therapeutic strategies for these patients. Aim. The aim of this study was to find if these changes influenced survival of individuals with proximal cholangiocarcinoma. Material. 627 individuals with a diagnosis of cholangiocarcinoma (not including distal common duct cancer) during the period from 2000 to 2011 were registered in Sweden's Western Region. The material was divided into three consecutive time periods. Results. The overall survival curves for individuals with cholangiocarcinoma improved over the three time periods (n = 627)(P = 0.0013). Median survival increased from 2.6 months in the first period (2000-2003) to 3.6 months in the final four years (2008-2011). Patients with perihilar cholangiocarcinoma (PHC) had longer median survival than those with intrahepatic cholangiocarcinoma (IHC): 6.8 versus 3.2 months (P = 0.0003). An improvement in the survival curves over time was seen for those with IHC (P = 0.034) but not for patients with PHC (P = 0.38). Nine percent of the patients with IHC had potential curative surgical therapy. The three-year survival rate after liver resection for patients with IHC was 35% and 60% after liver transplantation. Among patients with PHC, 15.3% had potential curative bile duct resection with a concomitant liver resection and 6.1% bile duct resection alone. The three-year survival rate for these two groups was 32% and 20%, respectively. Conclusion. Overall survival for individuals with PHC was better than for those with IHC. Over time survival in IHC patients improved but not in those with PHC.
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| 8. |
- Lindner, Philip, et al.
(författare)
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Who seeks ICBT for depression and how do they get there? : effects of recruitment source on patient demographics and clinical characteristics
- 2015
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 2:2, s. 221-225
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Tidskriftsartikel (refereegranskat)abstract
- Studies on internet-administered cognitive behavior therapy (ICBT) frequently use several different sources of recruitment, yet no study has investigated whether different recruitment sources produce different clinical and demographic profiles among participants. Using data from a large sample (n = 982) seeking ICBT for depression, we compared these characteristics on the basis of self-reported recruitment source. Recruitment sources that imply more active treatment-seeking behaviors (Google searches, viewing postings on mental health websites) presented more severe depression and anxiety than those recruited through more passive sources of information (newspaper advertisements, referrals by friends and family). In addition, a number of demographic differences between groups were found. These findings have important implications for ICBT research projects and clinical programs who employ open recruitment procedures and multi-modal recruitment strategies, and who wish to recruit representative samples or target specific subgroups. Replications in other countries will however be required to establish cross-cultural patterns.
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| 9. |
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| 10. |
- Sternby Eilard, Malin, 1974, et al.
(författare)
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A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation
- 2019
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma.MethodsTwelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12weeks and thereafter every 8weeks. Toxicity and quality of life was assessed at 1 and 4weeks and every 4weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90days was registered according to Clavien-Dindo.ResultsBaseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired.ConclusionsThis study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study.Trial registrationEudraCT number: 2010-024306-36 (date 2011-04-07).
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