| 1. |
- Adwall, Linda, et al.
(författare)
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Prospective Evaluation of Complications and Associated Risk Factors in Breast Cancer Surgery
- 2022
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Ingår i: Journal of Oncology. - : Hindawi Publishing Corporation. - 1687-8450 .- 1687-8469. ; 2022
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Tidskriftsartikel (refereegranskat)abstract
- Background; Surgical site infection (SSI) is a well-known complication after breast cancer surgery. The primary aim was to assess risk factors for SSI. Risk factors for other wound complications were also studied.Materials and Methods: In this prospectively registered cohort study, patients who underwent breast-conserving surgery (BCS) or mastectomy between May 2017 and May 2019 were included. Data included patient and treatment characteristics, infection, and wound complication rates. Risk factors for SSI and wound complications were analyzed with simple and multiple logistic regression.Results: The study cohort consisted of 592 patients who underwent 707 procedures. There were 66 (9.3%) SSI and 95 (13.4%) wound complications. "BMI > 25, " "oncoplastic BCS, " "reoperation within 24 hour, " and "prolonged operative time " were risk factors for SSI with simple analysis. BMI 25-30 and > 30 remained as significant risk factors for SSI with adjusted analysis. Risk factors for "any wound complication " with adjusted analysis were "mastectomy with/without reconstruction " in addition to "BMI 25-30 " and "BMI > 30. "Conclusion: The only significant risk factor for SSI on multivariable analysis were BMI 25-30 and BMI > 30. Significant risk factors for "any wound complication " on multivariable analysis were "mastectomy with/without reconstruction " as well as "BMI 25-30 " and "BMI > 30. "
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| 2. |
- Annebäck, Matilda
(författare)
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Hypoparathyroidism after thyroid surgery- rates, risks, prevention and consequences
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypoparathyroidism is the most common complication after thyroid surgery and associated with short- and long-term consequences. The lack of a consensus on the definition of hypoparathyroidism has led to a broad range in the rates reported in the literature. The overall aim of this thesis was to study different aspects of hypoparathyroidism, in terms rates, risks and long-term impact. Paper I is a case control study, investigating prophylactic, preoperative treatment with active vitamin D and early hypocalcemia after total thyroidectomy. The study showed that patients with preoperative treatment had a lower risk of early hypocalcemia and a reduced length of stay in hospital, compared to patients without treatment. No adverse outcomes were found. Paper II is a population-based retrospective cohort study on the rate and risks for permanent hypoparathyroidism after total thyroidectomy for benign thyroid disease. Data was retrieved from The Swedish National Patient Register, The Swedish Quality Register for Thyroid, Parathyroid and Adrenal Surgery and The Swedish Prescribed Drug Registry. Permanent hypoparathyroidism was defined as dispensation of calcium and/or active vitamin D >12 months after surgery. Among 7852 patients, 12.5% developed permanent hypoparathyroidism. Surgery at low volume centers, parathyroid autotransplantation, female gender and high age were independent risk factors. In Paper III the aim was to validate the high rate of permanent hypoparathyroidism found in Paper II. A regional cohort was extrapolated from the national cohort. A retrospective chart review, of 1636 patients, was performed. Using a strict definition, 6.2 % were found to have definitive permanent hypoparathyroidism. Additionally, 2.5 % were found to have possible permanent hypoparathyroidism. Of these, at least 1.7 % might have been overtreated due to lacking attempts to unwind the treatment. The study also proposed that the rate of low early PTH in a cohort might be useful to predict the rate of permanent hypoparathyroidism. Paper IV investigated health related quality of life (HRQoL) in patients with and without permanent hypoparathyroidism using the same cohort as in Paper III and SF-36 v.2. No impact of definitive hypoparathyroidism on HRQoL could be found. In conclusion, the use of preoperative active vitamin D may be useful as a tool to lower the risk of early hypocalcemia. The risk of permanent hypoparathyroidism after total thyroidectomy is high and there is a need for improved follow up. Permanent hypoparathyroidism may not have a negative effect on HRQoL in most patients.
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| 3. |
- Annebäck, Matilda, et al.
(författare)
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Preoperative prophylactic active vitamin D to streamline total thyroidectomy
- 2022
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypocalcaemia is a common complication after total thyroidectomy (TT). Treatment consists of calcium and active vitamin D supplementation. Low levels of vitamin D before surgery have been shown to be a risk factor for postoperative hypocalcaemia, yet studies examining routine preoperative vitamin D supplementation have shown conflicting results. This retrospective cohort study aims to investigate the potential benefit of preoperative active vitamin D supplementation on hypocalcaemia and its symptoms after TT.MethodsThis study included patients undergoing TT at Uppsala University Hospital from January 2013 to December 2020, resulting in a total of 401 patients after exclusion. Routine preoperative alfacalcidol treatment was initiated for all TT patients in January 2017 resulting in two groups for comparison: one group (pre-January 2017) that was prescribed preoperative alfacalcidol and one that was not. Propensity score matching was used to reduce bias. The primary outcome was early postoperative hypocalcaemia (serum calcium, S-Ca less than 2.10 mmol/l); secondary outcomes were symptoms of hypocalcaemia and length of stay.ResultsAfter propensity score matching, there were 108 patients in each group. There were 2 cases with postoperative day one S-Ca less than 2.10 in the treated group and 10 cases in the non-treated group (P < 0.001). No patients in the treated group had a S-Ca below 2.00 mmol/l. Preoperative alfacalcidol was associated with higher mean serum calcium level day one (2.33 versus 2.27, P = 0.022), and reduced duration of hospital stay (P < 0.001). There was also a trend toward fewer symptoms of hypocalcaemia (18.9 per cent versus 30.5 per cent, P = 0.099).ConclusionsProphylactic preoperative alfacalcidol was associated with reduced biochemical hypocalcaemia and duration of hospital stay following TT. Also, with this protocol, it is suggested that routine day 1 postoperative S-Ca measurement is not required.
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| 4. |
- Annebäck, Matilda, et al.
(författare)
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Quality of life in patients with permanent hypoparathyroidism after thyroidectomy: a population-based study with long-term follow up
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIn recent years, several studies have shown that permanent hypoparathyroidism has a negative impact on health-related quality of life (HRQoL). However, these results could have been affected by short-term follow up, selection bias and confounding factors. The aim of this study was to investigate HRQoL in patients with and without permanent hypoparathyroidism after total thyroidectomy for benign thyroid disease, using a strict definition of permanent hypoparathyroidism and long-term follow up data. A secondary aim was to evaluate if permanent hypoparathyroidism affects the risk of death.Material and MethodsAll patients who underwent total thyroidectomy in a region of Sweden between 2005 and 2015 were assessed for eligibility. All eligible patients were invited to participate in the study through by letter on August, 2021. SF-36v.2 was used to compare HRQoL in patients with and without permanent hypoparathyroidism. ResultsOut of 1636 patients, 1483 patients were invited to participate in the study. In total, 716 (48.3%) patients answered the SF-36v.2 questionnaire and were included in the study cohort. Mean follow-up was 10.9 (SD ±3.2) years. Patients with and without permanent hypoparathyroidism did not differ in baseline characteristics, with the exception that patients with permanent hypoparathyroidism were younger. No difference was found in HRQoL between the groups regarding all health domains and the summary component scores (p>0.05). Survival analysis revealed no increased risk of death in patients with permanent hypoparathyroidism.ConclusionsNo difference in HRQoL was found when comparing patients with and without permanent hypoparathyroidism after total thyroidectomy for benign thyroid disease on long-term follow up. Permanent hypoparathyroidism did not affect mortality in the present study; however, this needs to be further investigated in larger studies
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| 5. |
- Annebäck, Matilda, et al.
(författare)
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Risk of Permanent Hypoparathyroidism After Total Thyroidectomy for Benign Disease : A Nationwide Population-based Cohort Study From Sweden
- 2021
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:6, s. e1202-e1208
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the prevalence and risk factors for permanent hypoparathyroidism after total thyroidectomy for benign disease in a population-based setting with data independent of input of complication data.SUMMARY OF BACKGROUND DATA: The reported rate of permanent hypoparathyroidism is highly variable and mostly rely on reported complication data from national or institutional registries.METHODS: All patients who underwent total thyroidectomy in Sweden from 2005 to 2015 were identified through Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery and the Swedish National Patient Register. Patients were matched to outcome data from the Swedish Prescribed Drug Register. Permanent hypoparathyroidism was defined as treatment with calcium and/or active vitamin D more than 1 year after surgery.RESULTS: Seven thousand eight hundred fifty-two patients were included and 938 (12.5%) developed permanent hypoparathyroidism. The risk was lower in patients registered in the quality register (11.0% vs 16%, P < 0.001). In a multivariable analysis there was a higher risk of permanent hypoparathyroidism in patients with parathyroid autotransplantation [Odds ratio (OR) 1.72; 95% confidence interval 1.47-2.01], center-volume <100 thyroidectomies per year (OR 1.22; 1.03-1.44), age above 60 year (OR 1.64; 1.36-1.98) and female sex (OR 1.27; 1.05-1.54). Reported data from the quality register only identified 178 of all 938 patients with permanent hypoparathyroidism.CONCLUSION: The risk of permanent hypoparathyroidism after total thyroidectomy was high and associated with parathyroid autotransplantation, higher age, female sex and surgery at a low volume center. Reported follow-up data might underestimate the rate of permanent hypoparathyroidism.
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| 6. |
- Annebäck, Matilda, et al.
(författare)
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Validating the risk of hypoparathyroidism after total thyroidectomy in a population-based cohort : plea for improved follow-up
- 2024
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA previous nationwide study from Sweden showed that the rate of permanent hypoparathyroidism is high and under-rated in the Swedish Quality Register. This retrospective population-based study aimed to validate the rate and diagnosis of permanent hypoparathyroidism found in the previous study. A secondary aim was to assess the relationship between the rate of low parathyroid hormone (PTH) levels within 24 h after surgery and the rate of permanent hypoparathyroidism.MethodsAll patients who underwent total thyroidectomy from 2005 to 2015 in a region of Sweden were included. Data were retrieved from local health records, the National Patient Registry, the Swedish Prescribed Drug Registry, and the Swedish Quality Register. A strict definition of permanent hypoparathyroidism was used, including biochemical data and attempts to stop the treatment.ResultsA total of 1636 patients were included. Altogether, 143 patients (8.7 per cent) developed permanent hypoparathyroidism. Of these, 102 (6.2 per cent) had definitive permanent hypoparathyroidism, whereas 41 (2.5 per cent) had possible permanent hypoparathyroidism, because attempts to stop the treatment were lacking (28) or patients were lost to follow-up (13). The agreement between the Swedish Quality Register and the chart review was 29.3 per cent. A proportion of 23.2 per cent with a PTH level below the reference value corresponded to a 6.7 per cent rate of permanent hypoparathyroidism.ConclusionThe risk of permanent hypoparathyroidism after total thyroidectomy is high. Some patients are overtreated because attempts to stop the treatment are lacking. Quality registers might underestimate the risk of permanent hypoparathyroidism. Approximately one-quarter of all patients with low PTH levels immediately after surgery developed permanent hypoparathyroidism.
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| 7. |
- Backman, Samuel, et al.
(författare)
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Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:2, s. 705-712
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Tidskriftsartikel (refereegranskat)abstract
- Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
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| 8. |
- Backman, Samuel, 1994-
(författare)
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Molecular studies of endocrine tumors : Insights from genetics and epigenetics
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endocrine tumors may be benign or malignant and may occur in any of the hormone producing tissues. They share several biological characteristics, including a low mutation-burden, and may co-occur in several hereditary tumor syndromes. The aim of this thesis was to identify genetic and epigenetic aberrations in endocrine tumors.In paper I we performed a comprehensive DNA methylation analysis of 39 pheochromocytomas/paragangliomas as well as 4 normal adrenal medullae on the HumanMethylation27 BeadChip array. We validated two previously described clusters based on DNA methylation with distinct genetic associations.In Paper II we performed a transcriptomic analysis of 15 aldosterone producing adenomas. CTNNB1-mutated tumors were found to form a distinct subgroup based on gene expression and to share gene expression similarities with non-aldosterone producing adrenocortical tumors with CTNNB1 mutations, including overexpression of AFF3 and ISM1.In paper III we used whole genome sequencing to identify germline genetic variants in 14 patients with Multiple Endocrine Neoplasia type 1 previously found to be wildtype for the MEN1 gene on routine clinical testing. Three patients were found to carry previously undetected MEN1 mutations. Two patients were confirmed to have phenocopies caused by variants affecting CASR or CDC73. In total 9/14 patients were not found to have a disease-causing germline variant, suggesting that the syndrome may in some cases be due to chance co-occurrence of several sporadic tumors.In paper IV RNA-Seq and whole genome sequencing of a cohort of SI-NETs selected on the basis of unusually short or long survival was performed in order to identify disease causing genes and potential prognostic factors. We confirmed known genetic aberrations and found rare variants in known cancer driver genes. Based on gene expression two clusters that differ in prognosis were detected. Moreover, through integration of copy number variation data and gene expression, we identied novel potential disease causing genes.
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| 9. |
- Backman, Samuel, et al.
(författare)
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Potential prognostic markers and candidate genetic drivers in small intestine neuroendocrine tumours
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundSmall intestinal neuroendocrine tumours (SI-NETs) are the most common tumour of the small intestine. The disease often has a favourable outcome with long survival even in the context of metastatic disease. However, some patients fare worse and succumb to the disease soon after diagnosis despite similar stage and grade. Molecular prognostic markers are lacking. The most common genetic aberration is loss of chromosome 18q, although the oncogenic mechanism of this is unknown. The only recurrently mutated gene is CDKN1B, which is mutated in 9% of cases.AimsTo identify molecular derangements in SI-NETs and identify potential prognostic markers.MethodsForty tumour samples from thirty patients with unusually long or unusually short survival after diagnosis were subjected to whole genome sequencing. Twenty of the samples were also included for RNA Sequencing.ResultsIn addition to mutations in CDKN1B we find rare variants in known cancer genes including NF1, MAX and SPEN. Unsupervised clustering based on gene expression resulted in two clusters with prognostic significance. We identify potential prognostic markers based on gene expression. Finally, we identify genes whose expression is affected by the most common copy number variations in these tumours, including SOCS6 on chromosome 18 and ATM on chromosome 11.
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| 10. |
- Barazeghi, Elham, et al.
(författare)
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5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma
- 2016
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80-85 %) or multiglandular disease (similar to 15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1-5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1. Results: The global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth. Conclusions: 5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.
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