| 1. |
- Aberg, Fredrik, et al.
(författare)
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Differences in long-term mortality among liver transplant recipients and the general population: A population-based Nordic study.
- 2015
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 61:2, s. 668-677
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Tidskriftsartikel (refereegranskat)abstract
- Dramatic improvement in first-year outcomes post-liver transplantation (LT) has shifted attention to long-term survival, where efforts are now needed to achieve improvement. Understanding the causes for premature death is a prerequisite for improving long-term outcome. Overall and cause-specific mortality of 3299 Nordic LT patients (1985-2009) having survived 1 year post-LT were divided by expected rates in the general population, adjusted for age, sex, calendar time, and country to yield standardized mortality ratios (SMRs). Data came from the Nordic Liver-Transplant Registry and WHO mortality-indicator database. Stagnant patient survival rates >1 year post-LT were 21% lower at 10 years than expected survival for the general population. Overall SMR for death before age 75 (premature mortality) was 5.8 (95%CI 5.4-6.3), with improvement from 1985-1999 to 2000-2010 in hepatitis C (HCV) (SMR change 23.1-9.2), hepatocellular carcinoma (HCC) (SMR 38.4-18.8), and primary sclerosing cholangitis (SMR 11.0-4.2), and deterioration in alcoholic liver disease (8.3-24.0) and acute liver failure (ALF) (5.9-7.6). SMRs for cancer and liver disease (recurrent or transplant-unrelated disease) were elevated in all indications except primary biliary cirrhosis (PBC). Absolute mortality rates underestimated the elevated premature mortality from infections (SMR 22-693) and kidney disease (SMR 13-45) across all indications, and from suicide in HCV and ALF. SMR for cardiovascular disease was significant only in PBC and alcoholic liver disease, owing to high mortality in the general population. Transplant-specific events caused 16% of deaths. Conclusion: standardized premature mortality provided an improved picture of long-term post-LT outcome, showing improvement over time in some indications, not revealed by overall absolute mortality rates. Causes with high premature mortality (infections, cancer, kidney and liver disease, and suicide) merit increased attention in clinical patient follow-up and future research. (Hepatology 2014;).
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| 2. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Interventional treatment of gastrointestinal neuroendocrine tumours.
- 2000
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Ingår i: Digestion. - 0012-2823. ; 62 Suppl 1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.
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| 3. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Interventional treatment of the carcinoid syndrome
- 2004
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Ingår i: Neuroendocrinology. - 0028-3835. ; 80 Suppl 1, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Liver metastases imply a major problem in patients with carcinoid tumours and hormone overproduction. Patients with distant metastases can undergo resection for potential cure or for symptom palliation. In patients with bilobar liver metastases other interventions are at hand, e.g. local ablation or hepatic arterial embolization. In selected cases liver transplantation can be a treatment alternative. Prior to all interventions patients with midgut carcinoids are protected with somatostatin analogues to reduce hormone secretion. Patients with foregut carcinoids may present special problems with life-threatening release of histamine during interventions.
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| 4. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Liver transplantation for treatment of metastatic neuroendocrine tumors
- 2004
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923. ; 1014, s. 265-9
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation can be considered a therapeutic option for patients with neuroendocrine tumors only metastatic to the liver. Important selection criteria are well-differentiated tumors and a low proliferation rate (Ki67 <10%). In this series, orthopic liver transplantation offered good relief of symptoms and long disease-free intervals with initial survival of grafts and patients as in benign disease. The experience with multivisceral transplantation is still limited.
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| 5. |
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| 6. |
- Backman, L., et al.
(författare)
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Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:8, s. 2654-6
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Tidskriftsartikel (refereegranskat)abstract
- This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.
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| 7. |
- Banerjee, Debashish, et al.
(författare)
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Characterization of Decellularized Implants for Extracellular Matrix Integrity and Immune Response Elicitation
- 2022
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Ingår i: Tissue Engineering Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 28:13-14, s. 621-639
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Tidskriftsartikel (refereegranskat)abstract
- Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. Impact StatementThe development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.
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| 8. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources.
- 2010
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Ingår i: Environmental research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 110:1, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. OBJECTIVES: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. METHODS: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. RESULTS: The median kidney concentrations were 12.9microg/g (wet weight) for cadmium, 0.21microg/g for mercury, and 0.08microg/g for lead. Kidney Cd increased by 3.9microg/g for a 10 year increase in age, and by 3.7microg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5microg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. CONCLUSIONS: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.
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| 9. |
- Berg, Malin, 1976, et al.
(författare)
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Replacement of a Tracheal Stenosis with a Tissue-Engineered Human Trachea Using Autologous Stem Cells: A Case Report
- 2014
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Ingår i: Tissue Engineering. Part A. - 1937-3341 .- 1937-335X. ; 20:1-2, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based therapies, involving tissue engineering represent interesting and potentially important strategies for treatment of patients with various disorders. Here, using a detergent-enzymatic method we prepared an intact 3-dimensional scaffold of an extracellular matrix (ECM) derived from a human cadaver donor trachea, which we repopulated with autologous stem cells and implanted into a 76-year old patient with tracheal stenosis including lower part of the larynx. Although the graft provided the patient with an open airway, a week after surgery, the mucous membrane of the graft was covered by a 1-2mm thick fungal infection, which was treated with local and systemic anti-fungal therapy. The airway lumen was postoperatively controlled by fiberbrandoscopy and found stable and sufficient. However, twenty-three days later the patient died due to cardiac arrest but with a patent, open, stable tracheal transplant and intact anastomoses. Histopathological results of the transplanted tracheal graft at autopsy showed a squamous but not ciliated epithelium, neovascularization, bundles of -sma positive muscle cells, serous glands and nerve fibres with S-100 positive nerve cells in the submucosa and intact chondrocytes in the cartilage. Our findings suggest that although autologous stem cells- engineered tracheal matrices may represent a tool for clinical tracheal replacement. Further preclinical studies are required for generating functional airway grafts and long term effects of such grafts.
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| 10. |
- Björnsson, Einar, 1958, et al.
(författare)
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Long-term follow-up of patients with alcoholic liver disease after liver transplantation in Sweden: impact of structured management on recidivism
- 2005
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Ingår i: Scandinavian journal of gastroenterology. - 0036-5521. ; 40:2, s. 206-16
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: No systematic evaluation has been performed previously in the Scandinavian countries on patients transplanted for alcoholic liver disease (ALD). Data are limited on the impact of structured management of the alcohol problem on the risk of recidivism following transplantation in ALD. MATERIAL AND METHODS: A total of 103 ALD patients were compared with a control group of patients with non-alcoholic liver disease (NALD). The recidivism rates for ALD patients transplanted between 1988 and 1997 as well as after 1998 (institution of structured management) were compared. RESULTS: The median follow-up was 31 (6-60) months in the ALD group and 37 (12-63) months in the control group (NS). The overall survival rates at 1- and 5 years were, respectively, 81% and 69% for the ALD group and 87% and 83% for the non-alcoholic group. The proportion of patients with Child-Pugh C (75%) was higher in ALD patients than in NALD patients (44%) (p<0.01). Thirty-two (33%) ALD patients resumed taking some alcohol after transplantation; 17 patients (18%) were heavy drinkers. A multivariate analysis showed that: sex, age, marital and employment status, benzodiazepine use and a history of illicit drug abuse did not predict the risk of alcohol relapse post-Tx. Nineteen out of 40 (48%) patients transplanted before the start of structured management had resumed alcohol but 13 (22%) out of 58 after this intervention (p=0.002). CONCLUSIONS: ALD is a good indication for liver transplantation, with similar results in the ALD patients. Structured management of the alcohol problem before and after transplantation is important in minimizing the risk of recidivism.
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