| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Almobarak, Bilal, et al.
(författare)
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Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype
- 2023
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSmall intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location.MethodsClinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology.ResultsTumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology.ConclusionOur results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor.
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| 3. |
- Almquist, Martin, et al.
(författare)
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Surgical management of cytologically indeterminate thyroid nodules
- 2019
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Ingår i: Gland Surgery. - : AME Publishing Company. - 2227-684X .- 2227-8575. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Nodules in the thyroid are frequent. Preoperative investigations including fine-needle cytology and ultrasound cannot in all patients rule out malignancy. Thus, surgical excision for histopathologic examination is often needed. In this narrative review, we examine aspects of the surgical management of indeterminate thyroid nodules, using a comprehensive review of the available literature. The authors manually searched PubMed for relevant literature, including recently published guidelines. Hemithyroidectomy without lymph node dissection remains the recommended management in indeterminate thyroid nodules, i.e., the complete removal of one lobe of the thyroid, for indeterminate thyroid nodules, defined as nodules with fine-needle cytology fulfilling the criteria of Bethesda III or IV categories. At surgery, it is important to preserve the recurrent and superior laryngeal nerves, and intraoperative neuromonitoring is a useful adjunct. Recent data also suggest that parathyroid autofluorescent techniques are promising tools for parathyroid preservation. There is still lack of specific preoperative investigations to rule in or out central lymph node metastasis. Intraoperative frozen section of lymph nodes can be valuable, but prophylactic or diagnostic central lymph node dissection is not routinely recommended. Outcomes after thyroid surgery arc better with high-volume surgeons and institutions. Surgery is probably best performed by high-volume surgeons in institutions with on-site expert pathologists and with technical adjuncts available for nerve and parathyroid preservation. Day-care surgery may be an option for selected patients.
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| 4. |
- Bergenfelz, Anders, et al.
(författare)
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Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial
- 2023
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Ingår i: The British journal of surgery. - 1365-2168 .- 0007-1323. ; 110:12, s. 1824-1833
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. METHODS: This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. RESULTS: Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. CONCLUSION: The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients.
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| 5. |
- Berndsen, Marta, 1986, et al.
(författare)
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Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy
- 2023
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Ingår i: The British journal of surgery. - 1365-2168. ; 110:12, s. 1857-1862
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS: This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS: The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION: Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.
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| 6. |
- Droeser, R. A., et al.
(författare)
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Hypoparathyroidism after total thyroidectomy in patients with previous gastric bypass
- 2017
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Ingår i: Langenbecks Archives of Surgery. - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 402:2, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Case reports suggest that patients with previous gastric bypass have an increased risk of severe hypocalcemia after total thyroidectomy, but there are no population-based studies. The prevalence of gastric bypass before thyroidectomy and the risk of hypocalcemia after thyroidectomy in patients with previous gastric bypass were investigated. Methods By cross-linking The Scandinavian Quality Registry for Thyroid, Parathyroid and Adrenal Surgery with the Scandinavian Obesity Surgery Registry patients operated with total thyroidectomy without concurrent or previous surgery for hyperparathyroidism were identified and grouped according to previous gastric bypass. The risk of treatment with intravenous calcium during hospital stay, and with oral calcium and vitamin D at 6 weeks and 6 months postoperatively was calculated by using multiple logistic regression in the overall cohort and in a 1:1 nested case-control analysis. Results We identified 6115 patients treated with total thyroidectomy. Out of these, 25 (0.4 %) had undergone previous gastric bypass surgery. In logistic regression, previous gastric bypass was not associated with treatment with i.v. calcium (OR 2.05, 95 % CI 0.48-8.74), or calcium and/or vitamin D at 6 weeks (1.14 (0.39-3.35), 1.31 (0.39-4.42)) or 6 months after total thyroidectomy (1.71 (0.40-7.32), 2.28 (0.53-9.75)). In the nested case-control analysis, rates of treatment for hypocalcemia were similar in patients with and without previous gastric bypass. Conclusion Previous gastric bypass surgery was infrequent in patients undergoing total thyroidectomy and was not associated with an increased risk of postoperative hypocalcemia.
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| 7. |
- Elias, Erik, 1979, et al.
(författare)
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Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine.
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several tumors clustered together in a limited intestinal segment. SI-NET also shows an unusual absence of driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determine the complete genome sequences of 61 tumors and metastases from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within single patients. Intra-individual comparisons revealed a lack of shared somatic single-nucleotide variants among the sampled intestinal lesions, supporting an independent clonal origin. Furthermore, in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from a cancer-priming local factor.
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| 8. |
- Gkaniatsa, Eleftheria, et al.
(författare)
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Adrenal venous sampling in young patients with primary aldosteronism. Extravagance or irreplaceable?
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:5
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Tidskriftsartikel (refereegranskat)abstract
- Current clinical guidelines suggest that adrenal venous sampling (AVS) may not be mandatory in young patients with primary aldosteronism (PA) and a solitary adrenal adenoma on imaging.The aim of this study was to further elucidate whether conventional imaging alone is sufficient to distinguish unilateral from bilateral PA among patients aged 40 years or younger.This was a retrospective study where data from 45 patients with PA, aged between 26 and 40 years, who underwent successful AVS between 2005 and 2019, were analyzed. Results concerning laterality on imaging studies and AVS were recorded. Outcome in surgically treated patients was assessed according to the Primary Aldosteronism Surgical Outcomes (PASO) criteria.In four of 25 patients with unilateral aldosterone production according to AVS, CT inaccurately suggested bilateral disease. Following unilateral adrenalectomy, all four patients showed complete clinical success. Five of 20 patients with bilateral aldosterone production according to AVS had a solitary adrenal nodule (8-19mm) on imaging. Two of these five patients were treated with unilateral adrenalectomy, neither having complete biochemical and/or clinical success postoperatively. Two of 16 patients younger than 35 years had discordant results, one with unilateral, and one with bilateral aldosterone production, according to AVS.Imaging studies inaccurately predicted laterality in a significant number of young patients with PA. In contrast to current clinical guidelines, our results support AVS for subtype evaluation in young adults with PA, including patients 35 years or younger.
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| 9. |
- Gkaniatsa, Eleftheria, et al.
(författare)
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Hip fractures in patients with primary aldosteronism - a Swedish nationwide study
- 2024
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Ingår i: OSTEOPOROSIS INTERNATIONAL. - 0937-941X .- 1433-2965.
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Tidskriftsartikel (refereegranskat)abstract
- In this large population-based matched cohort study, patients with primary aldosteronism were at increased risk of hip fracture, particularly subgroups traditionally considered at higher risk of osteoporosis such as women, patients older than 56 years at diagnosis, patients with established cardiovascular disease at diagnosis, and patients treated with MRA. Purpose Previous studies suggest that primary aldosteronism (PA) is associated with dysregulated bone homeostasis. The aim of this study was to evaluate the incidence of hip fractures in patients with PA. Methods We studied a nationwide cohort of 2419 patients with PA (1997-2019) and 24 187 age and sex matched controls from the general population. Hip fractures were identified by ICD codes in the Swedish National Patient Register. We estimated hazard ratios (HRs) for incident hip fractures, adjusted for prior fractures, socioeconomic factors, diabetes, osteoporosis, hyperparathyroidism, and cardiovascular disease (CVD). Pairwise subgroup comparisons were performed by age (18-56 and > 56 years), sex, CVD at baseline, and treatment for PA. Results During a mean follow up of 8 +/- 5 years, 64 (2.6%) patients had a hip fracture after being diagnosed with PA, compared to 401 (1.7%) controls. After adjustments, PA was associated with a 55% increased risk of hip fracture compared to controls (HR 1.55 [1.18-2.03]). HRs were increased in women (HR 1.76 [95% CI 1.24-2.52]), patients aged > 56 years (HR 1.62 [95% CI 1.21-2.17]), and patients with CVD at diagnosis (HR 2.15 [95% CI 1.37-3.37]). PA patients treated with adrenalectomy did not have higher risk than controls (HR 0.84 [95% CI 0.35-2.0]), while patients treated with mineralocorticoid receptor antagonists (MRA) retained a greater risk (HR 1.84 [95% CI 1.20-2.83]). Conclusion PA is associated with increased hip fracture risk, especially in women, patients diagnosed after the age of 56 years and patients with established CVD at diagnosis. Also, patients treated with MRA seem to have an increased risk of hip fractures, while adrenalectomy may be protective.
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| 10. |
- Gkaniatsa, Eleftheria, et al.
(författare)
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Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades -Yet An Underdiagnosed Disorder
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:9
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Tidskriftsartikel (refereegranskat)abstract
- Context: Primary aldosteronism (PA) is the most common cause of secondary hypertension.Yet, the incidence of PA in the general population has not been studied. Objective: To estimate the incidence of PA in the general population. Design and methods: Patients who had received a diagnostic code for PA between 1987 and 2016 were identified in the Swedish National Patient Registry. Assessment of clinical and biochemical data was used to validate the diagnosis. The annual incidence of PA was calculated by using the number of inhabitants in the Vastra Gotaland County as a reference. Results: Of 570 identified patients, 473 (83%) had confirmed PA. Eligible for the incidence analysis were 416 patients, 248 (60%) men and 168 (40%) women, diagnosed with PA between 1987 and 2016. The mean (+/- standard deviation) age at diagnosis was 56 +/- 12 years. The median (interquartile range) annual incidence was 2 (1-2) cases per million between 1987 and 1996, 6 (4-9) cases per million between 1997 and 2006 and 17 (12-24) cases per million between 2007 and 2016. At the end of the study (December 31, 2016), 386 patients with confirmed PA were alive and living in the Vastra Gotaland County, giving a prevalence of 231 cases per million (0.022%). Conclusions: Despite increasing incidence, the proportion of patients identified with PA is lower than expected. Given the serious consequences of untreated PA, the noticeably low prevalence at the end of the study stresses the need to increase the awareness of PA among health care providers.
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| 11. |
- Gkaniatsa, Eleftheria, et al.
(författare)
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Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study.
- 2023
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Ingår i: Hypertension (Dallas, Tex. : 1979). - 1524-4563. ; 80:12, s. 2601-2610
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Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities.We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]).Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality.Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.
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| 12. |
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| 13. |
- Gunnesson, Lisa, 1982, et al.
(författare)
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Maternal pheochromocytoma and childbirth in Sweden 1973-2015: a population-based study on short and long-term outcome
- 2024
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Ingår i: ENDOCRINE. - 1355-008X .- 1559-0100.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Data guiding management of pheochromocytoma and paraganglioma (PPGL) in pregnant women is limited, and long-term effects on the child are unknown. The aim of this retrospective registry-based case-cohort study was to assess how maternal PPGL and treatment impacts maternal and fetal outcome, including long-term outcome for the child. The main outcomes were maternal and fetal mortality and morbidity at delivery and relative healthcare consumption in children born by mothers with PPGL during pregnancy. Methods The National Birth Register identified 4,390,869 pregnancies between 1973-2015. Data was crosslinked with three Swedish national registers to identify women diagnosed with pheochromocytoma or paraganglioma within one year before or after childbirth. Hospital records were reviewed and register data was collected for five age-matched controls for each child until age 18. Results 21 women and 23 children were identified (incidence 4.8/1.000.000 births/year), all women with adrenal pheochromocytomas (Pc). The majority (71%) were diagnosed post-partum. Nine women (43%) were hypertensive during pregnancy. Preterm delivery was more common in Pc patients compared to controls (30% vs 6%, p < 0.001). There was no maternal or fetal mortality. Timing of tumor removal did not affect gestational weight or APGAR scores. There was no observed difference in hospital admissions between children affected by maternal Pc and controls. Conclusion Pc was commonly diagnosed after delivery and raised the risk of pre-term delivery, suggesting a need for an increased awareness of this diagnosis. However, reassuringly, there was no fetal or maternal mortality or any observed long-term impact on the children.
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| 14. |
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| 15. |
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| 16. |
- Hammarstedt, Lilian, et al.
(författare)
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Adrenal lesions in patients with extra-adrenal malignancy - benign or malignant?
- 2012
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Ingår i: Acta oncologica. - 1651-226X. ; 51:2, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background. Adrenal lesions in patients with extra-adrenal malignancy can be part of disseminated tumour disease, but may also be incidental, benign finding. Strict characterisation is therefore crucial, and may have profound effects on patient management. Purpose. To prospectively characterise and follow-up adrenal lesions in patients with extra-adrenal malignancy, stratified into those with past or concurrent malignancy, with or without metastases. Material and methods. All incidentally detected adrenal lesions identified at cross-sectional imaging during 18 months in a defined geographical region were prospectively reported. All adult oncologic patients with adrenal lesions were subjected to biochemical work-up and dedicated adrenal imaging for lesion characterisation, including a two year follow-up. Results. Benign adrenal lesions were found in 74% (29/39) of patients who had a history of extra-adrenal malignancy, in 53% (57/108) of those with concurrent extra-adrenal malignancy without metastatic disease and in 25% (27/109) in those with signs of metastatic disease. Conclusion. An adrenal lesion occurring in a patient with past malignancy has a high likelihood of representing a benign lesion, and even in patients with present signs of malignant disease at least one fourth to one half of such lesions are benign. Dedicated adrenal imaging including computed tomography attenuation measurements with wash-out characteristics, in addition to biochemical testing for adrenal dysfunction, is highly recommended in these cases, especially in patients without any other signs of metastatic spread.
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| 17. |
- Hammarstedt, Lilian, et al.
(författare)
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Adrenal lesions: variability in attenuation over time, between scanners, and between observers.
- 2013
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 54:7, s. 817-826
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMeasurements of attenuation (in Hounsfield units [HU]) and contrast wash-out are widely used to characterize adrenal lesions as benign or indeterminate/malignant at computed tomography (CT). Clinical experience suggests that such measurements of adrenal lesions may vary over time and between observers, making evaluation difficult.PurposeTo investigate the change over time of adrenal lesion size, attenuation, and contrast wash-out at CT, to determine inter-observer variability, and to analyze other factors underlying the variability.Material and MethodsIn a cohort of patients, with or without malignant disease, undergoing CT, adrenal lesions were prospectively analyzed. Lesions with growth >20% or >5 mm over 6 months were excluded. Non-enhanced attenuation and contrast medium wash-out over 2-year follow-up were analyzed. An inter-observer analysis with five observers and a phantom study of eight different CT scanners were performed to assess measurement variability.ResultsMean adrenal lesion non-enhanced attenuation values decreased by 0.5 HU/year during follow-up. Using 10 HU or 40% relative wash-out as threshold values for benign versus indeterminate lesions, 27 (20%) and 39 (29%) of 136 lesions, respectively, would be reclassified at some occasion during follow-up. In the observer analysis 37 of 40 lesions demonstrated agreement between all observers, using established threshold values. The phantom study showed an intra-scanner variability of 1-3 HU, but an inter-scanner variability of up to 8 HU for water.ConclusionThe clinically widespread use of specific attenuation threshold values for characterizing adrenal lesions must be used with great caution, considering that multiple factors, related to patient, equipment, scanning technique, and observer influence the outcome.
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| 18. |
- Isaksson, Elin, et al.
(författare)
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The Effect of Parathyroidectomy on Risk of Hip Fracture in Secondary Hyperparathyroidism
- 2017
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 41:9, s. 2304-2311
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Tidskriftsartikel (refereegranskat)abstract
- Secondary hyperparathyroidism increases the risk for fractures. Despite improvement in medical therapy, surgical parathyroidectomy (PTX) often becomes necessary, but its effect on risk of fractures is not clear. Our aim was to study the effect of parathyroidectomy on the risk of hip fractures in patients on dialysis or with a functioning renal graft at time of parathyroidectomy. In a cohort of 20,056 patients on dialysis or with functioning renal allograft, we identified 590 patients who underwent parathyroidectomy between 1991 and 2009. Of these, 579 were matched with 1970 non-PTX patients on age, sex, cause of renal disease and functioning renal allograft or not at the time of PTX or at the corresponding time for non-PTX patients (t). We calculated the risk for hip fracture after PTX using crude and adjusted Cox proportional hazards regressions, adjusting for time in renal replacement therapy before t, time with functioning renal allograft before and after t, comorbidity at t and a hip fracture before t. The adjusted hazard ratio (95% confidence interval) for hip fracture was 0.40 (0.18-0.88) for PTX patients, compared to non-PTX patients. When analyses were performed separately for sex, only women had a lower risk of hip fracture after PTX compared to non-PTX patients. The risk of hip fracture after PTX was similar in patients with or without functioning renal allograft at time for PTX. Parathyroidectomy is associated with a lower risk of hip fracture in female patients with secondary hyperparathyroidism.
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| 19. |
- Isaksson, Elin, et al.
(författare)
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Total versus subtotal parathyroidectomy for secondary hyperparathyroidism
- 2019
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Ingår i: Surgery. - : Elsevier BV. - 0039-6060. ; 165:1, s. 142-150
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Tidskriftsartikel (refereegranskat)abstract
- Background: It remains unclear whether total or subtotal parathyroidectomy for secondary hyperparathyroidism yields the best outcomes. We investigated mortality, cardiovascular events, hip fracture, and recurrent parathyroidectomy after total versus subtotal parathyroidectomy in patients on renal replacement therapy. Methods: Using the Swedish Renal Registry, the surgical registry for thyroid and parathyroid surgery, and the National Inpatient Registry, we identified patients who underwent parathyroidectomy between 1991 and 2013. We calculated the risk of outcome after total versus subtotal parathyroidectomy using COX's regression, adjusting for age, sex, cause of renal disease, time with a functioning graft before and after parathyroidectomy, Charlson comorbidity index, year of surgery, prevalent cardiovascular disease, time on dialysis, renal transplantation at parathyroidectomy, and treatment with calcimimetics before parathyroidectomy. Results: There were 824 patients who underwent parathyroidectomy, 388 total and 436 subtotal. There was no difference in mortality or risk of incident hip fracture between groups. Comparing the subtotal with the total parathyroidectomy, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 0.43 (0.25-0.72) and for recurrent parathyroidectomy 3.33 (1.33-8.32). Conclusion: There was a higher risk of cardiovascular events in patients after total parathyroidectomy compared with subtotal parathyroidectomy, but a lower risk of recurrent parathyroidectomy. (C) 2018 Elsevier Inc. All rights reserved.
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| 20. |
- Jabarkhel, Fatema, et al.
(författare)
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Primary Adrenal Leiomyosarcoma: Clinical, Radiological, and Histopathological Characteristics
- 2020
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Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Primary adrenal leiomyosarcoma (PAL) is a rare, high-grade proliferating mesenchymal tumor with a considerable risk of metastasis, deriving from the smooth muscle wall of a central adrenal vein, or its tributaries. Roughly 40 patients with PAL have been reported in the literature. Herein, we present 3 patients with incidentally discovered PAL, along with an overview of the current knowledge on the clinical, radiological, and histopathological characteristics of PAL. (C) Endocrine Society 2020.
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| 21. |
- Johansson, Gustav, et al.
(författare)
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Considerations and quality controls when analyzing cell-free tumor DNA
- 2019
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Ingår i: Biomolecular Detection and Quantification. - : Elsevier BV. - 2214-7535. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Circulating cell-free tumor DNA (ctDNA) is a promising biomarker in cancer. Ultrasensitive technologies enable detection of low (< 0.1%) mutant allele frequencies, a pre-requisite to fully utilize the potential of ctDNA in cancer diagnostics. In addition, the entire liquid biopsy workflow needs to be carefully optimized to enable reliable ctDNA analysis. Here, we discuss important considerations for ctDNA detection in plasma. We show how each experimental step can easily be evaluated using simple quantitative PCR assays, including detection of cellular DNA contamination and PCR inhibition. Furthermore, ctDNA assay performance is also demonstrated to be affected by both DNA fragmentation and target sequence. Finally, we show that quantitative PCR is useful to estimate the required sequencing depth and to monitor DNA losses throughout the workflow. The use of quality control assays enables the development of robust and standardized workflows that facilitate the implementation of ctDNA analysis into clinical routine. © 2019 The Authors
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| 22. |
- Johansson, Gustav, et al.
(författare)
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Monitoring circulating tumor DNA during surgical treatment in patients with gastrointestinal stromal tumors
- 2021
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 20:12, s. 2568-2576
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Tidskriftsartikel (refereegranskat)abstract
- The majority of patients diagnosed with advanced gastrointestinal stromal tumors (GISTs) are successfully treated with a combination of surgery and tyrosine kinase inhibitors (TKIs). However, it remains challenging to monitor treatment efficacy and identify relapse early. Here, we utilized a sequencing strategy based on molecular barcodes and developed a GIST-specific panel to monitor tumor-specific and TKI resistance mutations in cell-free DNA and applied the approach to patients undergoing surgical treatment. Thirty-two patients with GISTs were included, and 161 blood plasma samples were collected and analyzed at routine visits before and after surgery and at the beginning, during, and after surgery. Patients were included regardless of their risk category. Our GIST-specific sequencing approach allowed detection of tumor-specific mutations and TKI resistance mutations with mutant allele frequency < 0.1%. Circulating tumor DNA (ctDNA) was detected in at least one timepoint in nine of 32 patients, ranging from 0.04% to 93% in mutant allele frequency. High-risk patients were more often ctDNA positive than other risk groups (P < 0.05). Patients with detectable ctDNA also displayed higher tumor cell proliferation rates (P < 0.01) and larger tumor sizes (P < 0.01). All patients who were ctDNA positive during surgery became negative after surgery. Finally, in two patients who progressed on TKI treatment, we detected multiple resistance mutations. Our data show that ctDNA may become a clinically useful biomarker in monitoring treatment efficacy in patients with high-risk GISTs and can assist in treatment decision making.
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| 23. |
- Karakaya, Sinan, et al.
(författare)
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Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2 & alpha; correlate to an aggressive tumor phenotype. We show that HIF-2 & alpha; localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2 & alpha; was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2 & alpha; expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.
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| 24. |
- Kölby, Lars, 1963, et al.
(författare)
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Can quantification of VMAT and SSTR expression be helpful for planning radionuclide therapy of malignant pheochromocytomas?
- 2006
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 491-7
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-specific uptake of the radio-iodinated norepinephrine analogue meta-iodobenzylguanidine (MIBG) or uptake of radiolabeled somatostatin analogues via somatostatin receptors (SSTRs) are possibilities to diagnose and treat malignant pheochromocytomas/paragangliomas (PCs/PGs). The aims of this study were to investigate the quantitative expression of vesicular monoamine transporters (VMAT 1, 2) and all five SSTRs in malignant pheochromocytoma/paraganglioma (PC/PG) to evaluate the possibilities for tumor-specific radionuclide therapy. High scintigraphic 123I-MIBG uptake was found in two malignant PGs with high VMAT expression (500-730 copies of VMAT 1, 1,500-1,700 copies of VMAT 2 per 1,000 beta-actin), while no 123I-MIBG uptake was found in the malignant PG with low VMAT expression (330 copies of VMAT 1, 350 copies of VMAT 2 per 1,000 beta-actin). The two patients with high VMAT expression and high 123I-MIBG uptake were treated with 131I-MIBG (2-3x8 GBq). In vitro, the VMAT antagonist, reserpine, and the membrane pump inhibitor, clomipramine, inhibited the uptake of 123I-MIBG into tumor cells equally well (48% and 53% reduction respectively, P<0.001). SSTR2 was the most abundant receptor subtype, but in the two malignant PGs its expression was only 110-260 copies/1,000 beta-actin. The transporters at the cell membrane and in the vesicular membrane both appear to be of importance for the uptake of 123I-MIBG into malignant PC/PG. Quantitative determination of VMAT expression may be helpful in selecting patients suitable for radionuclide therapy with 131I-MIBG. The present data indicate that SSTR-mediated radionuclide therapy will not be effective treatment of malignant PC/PG.
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| 25. |
- Malvemyr, Per, et al.
(författare)
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Computed tomography for preoperative evaluation of need for sternotomy in surgery for retrosternal goitre.
- 2015
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Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2451. ; 400:3, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- The purposes of this study are to evaluate the usefulness of available CT classifications of retrosternal goitre (RSG) to identify patients needing sternotomy and to examine the effect of neck extension on goitre position.
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| 26. |
- Muth, Andreas, 1974, et al.
(författare)
-
Cohort study of patients with adrenal lesions discovered incidentally.
- 2011
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 98:10, s. 1383-91
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Tidskriftsartikel (refereegranskat)abstract
- This prospective cohort study investigated the incidence, clinical features and natural history of incidentally discovered adrenal mass lesions (adrenal incidentaloma, AI) in an unselected population undergoing radiological examination.
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| 27. |
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| 28. |
- Muth, Andreas, 1974, et al.
(författare)
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Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:2, s. 187-204
-
Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.
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| 29. |
- Muth, Andreas, 1974
(författare)
-
Incidentally discovered adrenal tumours, adrenal metastases and pheochromocytomas - Clinical and epidemiological aspects.
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With increasing use of high resolution radiological imaging incidentally discovered adrenal tumours (adrenal incidentalomas, AI) have become a common clinical problem. The aim of work-up and follow-up of patients with AI is to detect malignant (primary or metastatic) and/or hormone-producing tumours. The frequency of AI, and the clinical and patient reported outcomes of a two-year follow-up programme for AI was investigated in an unselected population undergoing radiology at all departments of radiology in Western Sweden during 18 months. The results of surgery for adrenal metastasis, and the impact of background variables on survival was analysed in a consecutive series of patients treated at the Sahlgrenska University Hospital (1996-2007). Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare catecholamine-producing tumours originating from the adrenal medulla and sympathetic and parasympathetic ganglia that may be detected as AI. The frequency of germ-line mutations (in the RET-, SDHB-, SDHC-, SDHD- and VHL-genes) was studied in all living patients with Pheo and abdominal PGL with apparently sporadic presentation registered in the National Cancer Register for Western Sweden 1958-2009. At focused evaluation of abdominal computed tomography the frequency of AI was 4.5 %. In patients with AI (without extra-adrenal malignancy) 6.6 % were operated on suspicion of malignant or hormone-producing tumours; hormone-producing tumours were verified in 3.1 %. No primary adrenal malignancy was found. All patients with hormone-producing or malignant tumours were identified at first evaluation. Further follow-up had low impact on Health-Related Quality of Life, but did not confer any benefit. Surgery for adrenal metastasis was associated with low perioperative morbidity and mortality. Factors associated with prolonged survival were potentially curative surgery, tumour type, no previous surgery for metastases, and long disease-free interval. It should be considered for all patients with isolated adrenal metastasis, and may be part of the multi-modal treatment in disseminated disease. Germ-line mutations were found in 5.6 % of patients with apparently sporadic Pheo/abdominal PGL, which was fewer than in other published series. All mutations were seen in SDHB and RET. Notably, no patient with SDHB-mutation has evidence of malignant disease after 16-28 years follow-up, even though this genotype has been associated with a high rate of malignancy.
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| 30. |
- Muth, Andreas, et al.
(författare)
-
[Many adrenal incidentalomas are not adequately evaluated - updated guidelines to improve follow-up are presented].
- 2023
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 120
-
Tidskriftsartikel (refereegranskat)abstract
- The use of cross-sectional imaging in Sweden has increased more than twofold in the last 20 years. Inadvertently discovered adrenal lesions, adrenal incidentalomas, are reported in about one per cent of abdominal investigations. The first Swedish guidelines for the management of adrenal incidentalomas were published in 1996 and have since then been regularly revised. Still, data indicate that less than half of patients receive adequate follow-up. Here we comment on the newly updated guidelines and briefly review the recommended clinical and radiological work-up.
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| 31. |
- Muth, Andreas, 1974, et al.
(författare)
-
Nationellt vårdprogram för adrenala incidentalom - Programmet har harmoniserats med europeiska riktlinjer – ger förenklad handläggning av patienter.
- 2017
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114
-
Tidskriftsartikel (refereegranskat)abstract
- Swedish guidelines for the management of adrenal incidentalomas Adrenal incidentalomas are seen in about five percent of abdominal CT examinations, and in most cases represent non-hormone-producing adrenocortical adenomas, but hormone-producing or malignant lesions occur. Revised Swedish guidelines for the evaluation and management of adrenal incidentalomas based on recently published European guidelines are presented. The importance of a thorough radiological, clinical and biochemical initial evaluation is emphasized. Long-term biochemical follow-up is not recommended and use of CT contrast medium »washout« calculation is omitted. No radiological evaluation or follow-up indicated for adrenal incidentalomas <1 cm size. For patients with diagnosed lipid rich adenomas (≤ 10 HU) 1-4 cm in size no radiological follow-up is suggested after initial evaluation.
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| 32. |
- Muth, Andreas, 1974, et al.
(författare)
-
Patient-reported impacts of a conservative management programme for the clinically inapparent adrenal mass.
- 2013
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 44:1, s. 228-236
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess patient-reported impacts and health-related quality of life (HRQL) of a 2-year follow-up programme in a large cohort of patients with stationary, non-functioning, adrenal incidentalomas (AIs) in western Sweden. 145 patients (mean age 68years, 62% females) with AI from a prospective study in western Sweden were studied. All had completed a 2-year follow-up programme by November 2007, without evidence of adrenal malignancy or hormone over-production. To evaluate patient-reported impacts and HRQL, an eight-item adrenal incidentaloma impact questionnaire was used retrospectively, together with the hospital anxiety and depression scale, and the short form-36. There were 111 patients (mean age 67years, 63% females) who responded to the questionnaire (response rate 77%). 77% reported that the AI diagnosis had caused them to be worried; however, fewer than 20% had thought about the lesion often during the follow-up programme, and only 3% had felt that it had a large impact on their current daily life. Only 4% stated that the follow-up programme had been a negative experience, nevertheless 10% reported a negative impact on their HRQL during the follow-up programme. Only 2% stated that release from follow-up caused worry to any degree. In total, 29% had possible anxiety, and 30% had possible depression, probably reflecting significant co-morbidity. Possible anxiety correlated with a more negative experience of the follow-up programme. In conclusion, the 2-year follow-up programme for patients with AI was well tolerated. Nonetheless, a small number remained worried throughout follow-up, suggesting the need for tailored counselling in individual patients to ameliorate negative impacts of follow-up.
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| 33. |
- Muth, Andreas, 1974, et al.
(författare)
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Prevalence of Germline Mutations in Patients with Pheochromocytoma or Abdominal Paraganglioma and Sporadic Presentation: A Population-Based Study in Western Sweden.
- 2012
-
Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 36:6, s. 1389-94
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Germline mutations in the susceptibility genes RET, SDHB, SDHD, and VHL have been reported in 7.5-24% of patients with pheochromocytoma (Pheo) or paraganglioma (PGL) and sporadic presentation. The purpose of the present study was to establish population-based data on the frequency of germline mutations in patients with apparently sporadic Pheo or abdominal PGL in Western Sweden. METHODS: From the Swedish National Cancer Registry, all patients with Pheo or PGL in Western Sweden (population 1.72 million) registered between 1958 and 2009 were identified (n=256). Patients were characterized using register data, hospital records, and clinical interviews. All living patients with Pheo or abdominal PGL and sporadic presentation (n=81) were invited to genetic screening; 71 patients accepted. Germline mutations were investigated by using direct sequencing for point mutations in RET, SDHB, SDHD, and VHL, and multiplex ligation-dependent probe amplification for gross deletions in SDHB, SDHC, SDHD, and VHL. Plasma or urinary metanephrines and/or urinary catecholamines were used for biochemical follow-up. RESULTS: The prevalence of germline mutations was 5.6%. Mutations were only seen in RET (n=1) and SDHB (n=3). Notably, in the patients with SDHB mutations, no malignant phenotype was observed during a mean follow-up of 23.3years. CONCLUSIONS: The frequency of germline mutations in patients with apparently sporadic Pheo and abdominal PGL in Western Sweden was lower than in previous studies. Variations in reported frequencies of germline mutations in patients with clinically sporadic Pheo/PGL may reflect geographical differences or patient selection.
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| 34. |
- Muth, Andreas, 1974, et al.
(författare)
-
Prognostic factors for survival after surgery for adrenal metastasis.
- 2010
-
Ingår i: European journal of surgical oncology (EJSO). - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 36:7, s. 699-704
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: To better define the indications for adrenalectomy for adrenal metastasis we have analysed factors predicting survival in our institutional series. METHODS: A consecutive series of 30 patients undergoing adrenalectomy for metastasis (1996-2007), excluding patients with simultaneous ipsilateral renal cell carcinoma (RCC), was studied. Metastases were regarded as synchronous (<6 mo), or metachronous (>6 mo), depending on the interval after primary surgery. Survival was calculated from time of adrenalectomy and factors influencing survival were identified. RESULTS: The tumour diagnoses were RCC n = 9, malignant melanoma n = 5, non-small-cell lung cancer n = 5, colorectal carcinoma n = 4, foregut carcinoid n = 2, adrenocortical carcinoma, breast cancer, hepatocellular carcinoma, urothelial carcinoma, and liposarcoma (one each); nine adrenal metastases were synchronous and 21 metachronous. Ten patients had undergone previous surgery for extra-adrenal metastases. Out of 30 adrenalectomies 10 were laparoscopic (LAdx) and 20 open (OAdx) procedures without surgical complications. The local recurrence rate was low: LAdx 1/10, OAdx 1/20, and the median survival was 23 months. Independent prognosticators of favourable survival were adrenalectomy for potential cure (p = 0.01), no previous metastasis surgery (p = 0.02), and tumour type (p = 0.043), with better prognosis for patients with adrenal metastasis from colorectal carcinoma and RCC and worse prognosis in non-small-cell lung cancer and malignant melanoma. CONCLUSIONS: Surgery for adrenal metastasis is safe and the indication for this procedure in an individual patient can be supported by several prognostic factors. The survival benefit in patients with adrenalectomy for potential cure indicates a therapeutic value of adrenalectomy in selected patients.
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| 35. |
- Muth, Andreas, 1974, et al.
(författare)
-
Systematic review of surgery and outcomes in patients with primary aldosteronism.
- 2015
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 102:4, s. 307-17
-
Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism (PA) is the most common cause of secondary hypertension. The main aims of this paper were to review outcome after surgical versus medical treatment of PA and partial versus total adrenalectomy in patients with PA.
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| 36. |
- Papakokkinou, Eleni, et al.
(författare)
-
Adrenal venous sampling in patients with ACTH-independent hypercortisolism
- 2019
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 66:2, s. 338-348
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Purpose: To study the usefulness of adrenal venous sampling (AVS) in distinguishing unilateral from bilateral cortisol production in patients with ACTH-independent hypercortisolism and bilateral adrenal lesions, or morphologically normal adrenal glands. Methods: A retrospective analysis of ten consecutive patients with ACTH-independent hypercortisolism who underwent AVS at our institution between 2009 and 2017. Unilateral dominant cortisol production was defined as a side-to-side cortisol/aldosterone lateralization ratio >2. Results: Four of ten patients had overt Cushing’s syndrome. Of these, two had bilateral adrenal lesions on computed tomography and two had normal adrenal glands. One of the two patients with bilateral adrenal lesions had, based on the AVS, a unilateral dominant cortisol production. Following unilateral adrenalectomy the patient developed adrenal insufficiency. The other three patients were considered to have bilateral cortisol production and underwent bilateral adrenalectomy. Six patients had a mild autonomous cortisol secretion and bilateral adrenal lesions. Based on AVS, one patient was considered to have unilateral dominant cortisol production, underwent unilateral adrenalectomy and developed transient adrenal insufficiency postoperatively. Conclusions: AVS may contribute to appropriate treatment in patients with ACTH-independent hypercortisolism and bilateral adrenal lesions. In our series, AVS was helpful in the decision-making of two out of ten patients, avoiding chronic treatment with steroidogenesis inhibitors, or inappropriate bilateral adrenalectomy.
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| 37. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
-
Illness perspectives in patients with primary aldosteronism.
- 2022
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
-
Tidskriftsartikel (refereegranskat)abstract
- The burden of symptoms and treatment in patients with primary aldosteronism (PA), as well as the patients' experience of the health care is sparsely studied. The objectives of this study were to describe symptoms considered to be the most troublesome by patients with PA, and to explore health related worries and expectations following treatment.This was an explorative qualitative study where 25 patients with PA, diagnosed between 2017 and 2019, were included; 13 patients who had undergone adrenalectomy and 12 who were receiving medical treatment. Data was collected during six group interviews and analyzed using a thematic approach.Three main themes were identified: 1) Distress of the past, where the most important issues were struggle to receive a correct diagnosis, impaired well-being and the consumption of a large number of tablets, 2) Satisfaction after receiving a correct diagnosis, both in patients with unilateral and bilateral disease, but also dissatisfaction with lack of information about the disease, and 3) Future concerns, where worries about the long-term effects of PA on health in general dominated.Our findings illustrate several important issues related to PA where improvements in patient care are needed, including actions aiming at shortening the long diagnostic delay, a thorough information to the patients about the disease is of great importance, and that all patients with PA, regardless of treatment, would benefit from a structured long-term follow-up.
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| 38. |
|
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| 39. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
-
Primary aldosteronism is an underdiagnosed cause of hypertension. Important to find undiagnosed patients--effective treatment available : Primär aldosteronism är en under-diagnostiserad orsak till hypertoni - Viktigt hitta odiagnostiserade patienter - effektiv behandling finns.
- 2015
-
Ingår i: Läkartidningen. - 0023-7205. ; 112
-
Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism is the most common cause of secondary hypertension with an estimated prevalence of 5-13 % among patients with hypertension. The most common causes are aldosterone producing adrenal adenoma and idiopathic adrenal hyperplasia. Patients with primary aldosteronism have a higher prevalence of cardiovascular morbidity and mortality compared to patients with essential hypertension. An effective treatment is available for patients with primary aldosteronism, with mineralocorticoid receptor antagonists in bilateral, and minimal invasive adrenal surgery in unilateral disease, which emphasizes the importance of early detection, adequate diagnostic work-up and treatment. In this paper we give a short review of the etiology, pathophysiology, co-morbidities, screening, diagnostic work-up, treatment, and treatment outcomes of primary aldosteronism.
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| 40. |
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| 41. |
- Rocca, Aldo, et al.
(författare)
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Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis.
- 2023
-
Ingår i: BMJ open. - 2044-6055. ; 13:7
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated.The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA.A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal.CRD42022362506.
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| 42. |
- Sellgren, Fredrik, et al.
(författare)
-
Outcomes After Surgery for Unilateral Dominant Primary Aldosteronism in Sweden
- 2020
-
Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 44, s. 561-569
-
Tidskriftsartikel (refereegranskat)abstract
- Background Primary aldosteronism (PA) is the most common cause of secondary hypertension. Surgery is the mainstay of treatment for unilateral dominant PA, but reported cure rates varies. The aim of the present study was to investigate contemporary follow-up practices and cure rates after surgery for PA in Sweden. Methods Patients operated for PA and registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) 2009-2015 were identified. Patient data were extracted, and follow-up data (1-24 months) was recorded. Doses of antihypertensive medication and potassium supplementation were calculated using defined daily doses (DDD), and the Primary Aldosteronism Surgical Outcome (PASO) criteria were used to evaluate outcomes. Results Of 190 registered patients, 171 (47% female, mean age 53 years, median follow-up 3.7 months) were available for analysis. In 75 patients (44%), missing data precluded evaluation of biochemical cure according to the PASO criteria. Minimal invasive approach was used in 168/171 patients (98%). Complication rate (Clavien-Dindo >3a) was 3%. No mortality was registered. Pre/postoperatively 98/66% used antihypertensives (mean DDD 3.7/1.5). 89/2% had potassium supplementation (mean DDD 2.0/0) before/after surgery. Complete/partial biochemical and clinical success according to the PASO criteria were achieved in 92/7% and 34/60%, respectively. Conclusion In this study, reflecting contemporary clinical practice in Sweden complete/partial biochemical and clinical success after surgery for PA was 92/7% and 34/60%. Evaluation of biochemical cure was hampered by lack of uniform reporting of relevant outcome measures. We suggest mandatory reporting of surgical outcomes using the PASO criteria for all units performing surgery for PA.
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| 43. |
- Streit, Sven, et al.
(författare)
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Burden of cardiovascular disease across 29 countries and GPs' decision to treat hypertension in oldest-old.
- 2018
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724. ; 36:1, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences.DESIGN: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed.SETTING: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland.SUBJECTS: This study included 2543 GPs from 29 countries.MAIN OUTCOME MEASURES: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (≥50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country.RESULTS: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00-4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12-4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56-1.98).CONCLUSIONS: GPs' choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD burden and low life expectancy at age 60 were most likely to treat hypertension in oldest-old. Key Points • General practitioners (GPs) are in a clinical dilemma when deciding whether (or not) to treat hypertension in the oldest-old (>80 years of age). • In this study including 1947 GPs from 29 countries, we found that a high country-specific cardiovascular disease (CVD) burden (i.e. myocardial infarction and/or stroke) was associated with a higher GP treatment probability in patients aged >80 years. • However, the association was modified by country-specific life expectancy at age 60. While there was a positive association for GPs in countries with a low life expectancy at age 60, there was no association in countries with a high life expectancy at age 60. • These findings help explaining some of the large variation seen in the decision as to whether or not to treat hypertension in the oldest-old.
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| 44. |
- Streit, Sven, et al.
(författare)
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Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries.
- 2017
-
Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 17:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision.METHODS: Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP.RESULTS: The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs' decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48-0.59; ORs per country 0.11-1.78).CONCLUSIONS: Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.
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| 45. |
- Svensson, Ellinor, et al.
(författare)
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The incidence of insulinoma in Western Sweden between 2002 and 2019
- 2022
-
Ingår i: Annals of Gastroenterology. - : Hellenic Society of Gastroenterology. - 1108-7471 .- 1792-7463. ; 35:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background Insulinoma is a rare pancreatic neuroendocrine neoplasm with an incidence of 0.7-4 cases per million/year. Because of its rarity, epidemiological studies on insulinoma are few and limited by small sample sizes. An increasing incidence of insulinoma has recently been suggested. The primary aim of this study was to investigate the incidence of insulinoma in the Vastra Gotaland Region (VGR) of Sweden. Secondary aims were to evaluate clinical characteristics, diagnostic workup, management and outcome in patients diagnosed with insulinoma. Methods Medical records were reviewed for all patients in the VGR who had received an ICD10 diagnosis code of a benign (D13.7) and/or a malignant (C25.4) tumor in the endocrine part of the pancreas, of hypoglycemia (E.161), and/or a code of a fasting test (AB011), from 2002-2019. Results Forty-two patients with insulinoma were identified, 37 of whom (20 men) were residents in the VGR at the time of diagnosis, giving a mean annual incidence of 1.3 cases per million/year. The mean (istandard deviation) age at diagnosis was 56118 years. Six of the 37 (16%) patients had metastatic insulinoma and 2 patients (5%) had a confirmed multiple endocrine neoplasia type 1 syndrome. At preoperative workup, computed tomography and endoscopic ultrasound detected an insulinoma in 28/36 (78%) and 21/21 (100%) cases, respectively. Conclusions Insulinoma remains a rare tumor in the modern era. The recorded mean annual incidence of 1.3 cases per million/year is compatible with the reported incidence in Sweden during the 1980s. Our results do not support an increasing incidence of insulinoma.
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| 46. |
- Tomic, Tajana Tesan, et al.
(författare)
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MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression
- 2020
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors. © 2020 Tomic et al.
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| 47. |
- van der Ploeg, Milly A., et al.
(författare)
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Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients : a Survey Study Across 30 Countries
- 2019
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Ingår i: Journal of general internal medicine. - : Springer. - 0884-8734 .- 1525-1497. ; 34:9, s. 1751-1757
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Tidskriftsartikel (refereegranskat)abstract
- Background Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients. Objective To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients. Design We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment. Main Measures Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (ORadj) were calculated for GPs' advice to stop. Key Results Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99). Conclusions The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.
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| 48. |
- Wilzén, Annica, et al.
(författare)
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Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes.
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:9, s. 2201-11
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Tidskriftsartikel (refereegranskat)abstract
- One out of ten patients with pheochromocytoma (PCC) and paraganglioma (PGL) develop malignant disease. Today there are no reliable pathological methods to predict malignancy at the time of diagnosis. Tumors harboring mutations in the succinate dehydrogenase subunit B (SDHB) gene often metastasize but the sequential genetic events resulting in malignant progression are not fully understood. The aim of this study was to identify somatic mutations that contribute to the malignant transformation of PCC/PGL. We performed pair-wise (tumor-normal) whole-exome sequencing to analyze the somatic mutational landscape in five malignant and four benign primary PCC/sympathetic PGL (sPGL), including two biological replicates from each specimen. In total, 225 unique somatic mutations were identified in 215 genes, with an average mutation rate of 0.54 mutations/megabase. Malignant tumors had a significantly higher number of mutations compared to benign tumors (p
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| 49. |
- Wängberg, Bo, 1953, et al.
(författare)
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Malignant pheochromocytoma in a population-based study: survival and clinical results.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 512-6
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Tidskriftsartikel (refereegranskat)abstract
- One hundred fifty-four consecutive patients with pheochromocytoma (PC, n=137) or paraganglioma (PG, n=17) were treated at our unit. Twenty patients had MEN 2, 15 VRD, and 1 VHL tumors. Twelve had malignant tumors and were classified according to mode of presentation: (1) Distant metastases (n=4); three underwent surgical debulking (with chemotherapy in one); and three had 131I-MIBG therapy. Within 4 years two patients died of tumor progression. (2) Locally advanced disease (n=4), all resected for cure. (3) Malignancy disclosed during follow-up after adrenalectomy with "benign" histopathology (n=4). All patients in groups 2 and 3 developed recurrence 9 (1-17) years after primary surgery; four underwent resection, one remains tumor-free. The others were treated chronically with phenoxybenzamine, combined with 131I-MIBG in one. These eight patients were observed 20 (5-35) years after primary surgery and 11 (1-19) years after recurrence. This series is population-based and may better reflect the natural history of malignant PC/PG than the series from national referral centers. Active surgical treatment and phenoxybenzamine resulted in low tumor-related mortality in groups 2 and 3; five patients died 8-30 years after diagnosis, four of PC/PG (three from group 2 and one from group 3) and one of other causes. We propose tumor uptake studies (MIBG- and octreotide scintigraphy) in patients with nonresectable metastases; to select individual radionuclide therapy data on the expression of CA-transporters/somatostatin receptors may be helpful. To diagnose PC/PG early, screening of adrenal incidentalomas has been suggested. In a regional population-based prospective study, 503 incidentalomas were reported during 18 months, but only one patient with PG was identified.
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