| 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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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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Barazeghi, Elham, et al.
(författare)
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EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase in the enterochromaffin cells of the small intestine, we found high and differential expression of EZH2 in primary SI-NETs and corresponding metastases. Silencing EZH2 in the SI-NET cell line CNDT2.5 reduced cell proliferation and induced apoptosis. Furthermore, EZH2 knockout inhibited tumor progression in a CNDT2.5 SI-NET xenograft mouse model, and treatment of SI-NET cell lines CNDT2.5 and GOT1 with the EZH2-specific inhibitor CPI-1205 decreased cell viability and promoted apoptosis. Moreover, CPI-1205 treatment reduced migration capacity of CNDT2.5 cells. The EZH2 inhibitor GSK126 also repressed proliferation of CNDT2.5 cells. Recently, metformin has received wide attention as a therapeutic option in diverse cancers. In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation. Exposure of GOT1 three-dimensional cell spheroids to CPI-1205 or metformin arrested cell proliferation and decreased spheroid size. These novel findings support a possible role of EZH2 as a candidate oncogene in SI-NETs, and suggest that CPI-1205 and metformin should be further evaluated as therapeutic options for patients with SI-NETs.
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| 8. |
- Botling, Johan, et al.
(författare)
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High-grade progression confers poor survival in pancreatic neuroendocrine tumors
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:11-12, s. 891-898
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes PanNET differentiation and proliferation over time, and to correlate findings to overall survival (OS).PATIENTS AND METHODS: In this retrospective cohort study we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were re-evaluated with regard to tumor histopathology and Ki-67 index.RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1-38%), grade 1 n=8, grade 2 n=36, and grade 3 n=2. The median change in Ki-67 index (absolute value; follow-up - baseline) was +14% (range -11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n=24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (HR 3.89, 95% CI 1.91-7.94, P<0.001).CONCLUSIONS: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.
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| 9. |
- Eriksson, John, et al.
(författare)
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Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops
- 2021
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 110:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmo county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of "carcinoid tumor" were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.
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| 10. |
- Heidsma, Charlotte M, et al.
(författare)
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International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors
- 2022
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 112:6, s. 571-579
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors.METHODS: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence.RESULTS: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80).CONCLUSIONS: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com.
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