| 1. |
- Frühling, Petter, et al.
(författare)
-
Irreversible electroporation of hepatocellular carcinoma and colorectal cancer liver metastases : A nationwide multicenter study with short- and long-term follow-up
- 2023
-
Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 49:11
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications.Methods: All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival.Results: In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i. q.r. 14-26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2-31.8 months), and 35.0 months (95% CI 13.8-56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6-65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5-32.5 months), and for CRCLM 6.0 months (95% CI: 4.5-7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event.Conclusion: IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable.
|
|
| 2. |
- Galmén, Karolina, et al.
(författare)
-
Quantitative assessment of atelectasis formation under high frequency jet ventilation during liver tumour ablation : A computer tomography study
- 2023
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundHigh frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure.AimThe aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia.MethodIn this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area.ResultAtelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted.ConclusionAtelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.
|
|
| 3. |
- Johansen, Karin, 1990-
(författare)
-
Effects of Pancreatic Surgery : Quality of Life, Cost-effectiveness and Postoperative Results
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND Pancreatic operations are large procedures with high rates of complications and other potentially impactful consequences such as diabetes and pancreatic exocrine insufficiency. Due to this, and due to the fact that the operations are often occasioned by periampullary tumours with a poor prognosis, it is important to evaluate how the operations affect patients in terms of postoperative results and quality of life. In the constantly developing field of pancreatic surgery, it is also important to evaluate the cost-effectiveness of new methods. METHODS The first study was a register study including all patients in the Swedish National Pancreatic and Periampullary Cancer Registry with a diagnosis from 2010-2018 who underwent pancreaticoduodenectomy (PD). Patients were divided into age groups of <70, 70-79 and ≥80 years old and were compared regarding preoperative, perioperative and postoperative data as well as survival. The second and third studies were based on the randomized controlled trial LAPOP performed in Linköping from 2015-2019 where 60 patients were randomized 1:1 to open or laparoscopic distal pancreatectomy and followed for two years with repeated quality of life questionnaires. For the second study, the EORTC QLQ-C30 and PAN26 questionnaires were collected and compared between groups. For the third study, the EQ-5D questionnaire was used in a cost-effectiveness analysis together with costs collected from patients’ medical records, including all health care-related costs up to 2 years postoperatively. Nonparametric bootstrapping with 10 000 samples was performed to compare quality-adjusted life years (QALYs) and costs between groups. The fourth study was a qualitative interview study in which 20 patients undergoing total pancreatectomy (TP) from 2020-2021 in Linköping or Karolinska University Hospitals were interviewed 6-9 months postoperatively about symptoms and life changes after the operation. RESULTS In the first study, 2793 patients underwent PD in the study period, of which 1137 patients were 70-79 years of age, and 148 patients were ≥80 years of age. There were no significant differences between groups regarding short-term mortality or the rate of severe complications according to the Clavien-Dindo classification of complications. Patients in the two older groups had a worse preoperative condition and a higher rate of medical and some surgical complications postoperatively. In the LAPOP trial, 54 patients were included in the quality of life analysis. There was a significant difference in six of the quality of life-domains measured with QLQ-C30 and PAN26 with better results in the laparoscopic group. When comparing values at the two-year measurement, 3 domains had a significant difference and 16 domains a clinically relevant difference of 10 or more, all with better results in the laparoscopic group. In the cost-effectiveness analysis, 56 patients were included in the analysis. Mean health care costs were €3 863 lower in the laparoscopic group (95% CI: -€8 020 to €385), and the QALYs were 0.08 higher (95% CI: -0.09 to 0.25). In the bootstrap analysis, 79% of samples had higher QALYs and lower costs for the laparoscopic group, and 95% were in favour of laparoscopic resection with a cost-per-QALY threshold of €50 000. Patients undergoing total pancreatectomy voiced symptoms and life changes that revolved around the two main themes: ‘changes in everyday life’ and ‘psychological journey’. In the former, patients described the impact of diabetes, food intake, diarrhoea and the process of recovery, where diabetes in particular appeared to be challenging for some. In the second theme, patients outlined the diagnosis processing, the importance of support from family, friends and the health care system, and a need for more thorough information. CONCLUSIONS Despite a worse preoperative condition, elderly patients undergoing PD did not have an increase in short-term mortality or serious complications. With continued careful preoperative examination, in particular regarding cardiovascular comorbidity, octogenarians can likely safely continue to be offered to undergo PD. After distal pancreatectomy, there was a considerable difference between groups regarding postoperative quality of life in favour of the laparoscopic method, which seemed to remain as long as 2 years postoperatively. The laparoscopic method was also favoured in the cost-effectiveness analysis where it was associated with lower costs and higher QALYs. These results support the ongoing transition from open to minimally invasive distal pancreatectomies. After TP, patients struggle with a lack of support and education, particularly regarding their diabetes treatment. Efforts should be undertaken to improve and standardize the diabetes care for this group.
|
|
| 4. |
- Mahajan, Anubha, et al.
(författare)
-
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
|
|
| 5. |
- Vidarsson, Bjarni, 1979-
(författare)
-
Complications in bariatric surgery with focus on gastric bypass
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is rising in pandemic proportions. At present, one third of the world’s population has become overweight or obese, and estimates predict 60% in 2030. Thus, the problem is gigantic. Obesity is associated with numerous diseases such as diabetes, high blood pressure, sleep apnea and cancer. Untreated obesity decreases life expectancy by about 10 years. Gastric bypass has been one of the cornerstones of surgical treatment. Since 1994 this is done by laparoscopic technique (LRYGB)In this thesis, we have primarily used data from our national quality register, the Scandinavian Obesity Surgical Registry (SOReg), on patients that have been operated with LRYGB. In the first paper, we evaluated the use of a novel suture for closing the gastrojejunostomy (upper anastomosis). Paper II and III focused on incidence, risk factors, treatment and outcome of anastomotic leaks. Paper IV compares the weight results, quality of life, use of medications and healthcare consumption in patients suffering from a serious complication within 30 days after LRYGB.In Paper I, the use of the barbed suture resulted in shorter operative time compared to a standard polyfilament, without increased risk for complications. Paper II showed that the incidence of anastomotic leaks at the gastrojejunostomy was 0.6%. Risk factors were male sex, higher age (≥49 years), diabetes, conversion to open surgery and prolonged operative time (≥ 90 minutes). Almost all patients were reoperated and 1% died. Paper III showed that the incidence of small bowel leaks was 0.3% and these leaks were associated with prolonged operative time, and surgery at a low-volume centre for leaks at the enteroaenteral anastomosis. Surgical re-intervention was common. Paper IV showed that severe complications within 30 days postoperatively after LRYGB occurred in 2.9% of cases. Two years later, the patients still reported inferior quality of life and had a higher use of antidepressants, proton pump inhibitors and opioids compared to uncomplicated cases. The need for additional in-hospital care was higher, even after the first 30 days.In conclusion, the novel barbed suture reduced operative time without increasing risks. Anastomotic leaks are rare, but serious complications in LRYGB do affect the patient in numerous ways and increase healthcare costs.
|
|
| 6. |
- Weinstock, Joshua S, et al.
(författare)
-
Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
-
Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
|
|
