| 1. |
- Annebäck, Matilda, et al.
(author)
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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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In: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:1
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Journal article (peer-reviewed)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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| 2. |
- Carling, Tobias, et al.
(author)
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Parathyroid MEN 1 gene mutations in relation to clinical characteristics of non-familial primary hyperparathyroidism
- 1998
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:8, s. 2960-2963
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Journal article (peer-reviewed)abstract
- Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.
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| 3. |
- Daskalakis, Kosmas, et al.
(author)
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Association of a Prophylactic surgical approach to Stage IV Small Intestinal Neuroendocrine Tumors with Survival.
- 2018
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In: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 4:2, s. 183-189
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Journal article (peer-reviewed)abstract
- Importance: Primary tumor resection and mesenteric lymph node dissection in asymptomatic patients with stage IV Small Intestinal Neuroendocrine Tumors (SI-NETs) is controversial.Objective: To determine whether locoregional surgery performed at diagnosis in asymptomatic SI-NETs patients with distant metastases affects overall survival (OS), morbidity and mortality, length of hospital stay (LOS) and re-operation rates.Design: This investigation was a cohort study of asymptomatic patients with stage IV SI-NET, diagnosed between 1985 and 2015, using the prospective Uppsala database of SI-NETs and the Swedish National Patient Register. Patients included were followed until May 2016 and divided to a first group, which underwent Prophylactic Upfront Surgery within six months from diagnosis Combined with Oncological treatment (PUSCO group) and a second group, which was either treated non-surgically or operated later (Delayed Surgery As Needed Combined with Oncological treatment [DSANCO group]).Setting: A tertiary referral center with follow-up data from the Swedish National Patient Register.Participants: We included 363 stage IV SI-NET patients without any abdominal symptoms within 6 months from diagnosis, treated either with PUSCO (n=161) or DSANCO (n=202).Exposure: PUSCO vs DSANCO.Main Outcomes and Measures: Overall survival (OS), length of hospital stay (LOS), postoperative morbidity and mortality and re-operation rates measured from baseline. Propensity score match was performed between the two groups.Results: Two isonumerical groups (n=91) occurred after propensity score matching. There was no difference between groups in OS (PUSCO median 7.9 vs DSANCO 7.6 years; [hazard ratio] HR, 0.98; [95% CI, 0.70-1.37]; log-rank P=.93) and cancer-specific survival (median 7.7 vs 7.6 years, HR, 0.99; [95%CI, 0.71-1.40]; log-rank P=.99). There was no difference in 30-day mortality (0% in both matched groups) or postoperative morbidity (2% vs 1%; P>.99), LOS (median 73 vs 76 days; P=.64), LOS due to local tumor-related symptoms (median 7 vs 11.5 days; P=.81) or incisional hernia repairs (4% in both groups; P>.99). Patients from the PUSCO group underwent more re-operative procedures (14%) compared to the DSANCO group (3%) due to intestinal obstruction (P< .001).Conclusion: Prophylactic upfront locoregional surgery confers no survival advantage in asymptomatic stage IV SI-NET patients. Delayed surgery as needed seems to be comparable in all examined outcomes, whilst offering the advantage of less re-operations for intestinal obstruction. The value of a priori locoregional surgery in the presence of distant metastases is challenged and needs to be elucidated in a randomized controlled study.
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| 4. |
- Fjällskog, Marie-Louise, et al.
(author)
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Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas
- 2007
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:6, s. 741-746
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Journal article (peer-reviewed)abstract
- Platelet-derived growth factor receptor (PDGFR) beta signaling is involved in autocrine growth stimulation of tumor cells, tumor angiogenesis and regulation of tumor interstitial fluid pressure. Development of PDGFR antagonists has further increased the interest for PDGFR as targets for anticancer treatments. Malignant endocrine pancreatic tumors (EPTs) express PDGFR beta both in stroma and on tumor cells. To investigate the role of PDGFR beta signaling in EPTs we compared PDGFR beta expression in normal endocrine pancreas to malignant EPTs and metastases. PDGFR beta expression was examined by immunohistochemistry using specific polyclonal antibodies in ten tissue samples from normal endocrine pancreas, 21 from primary EPTs and 19 from metastases. In eight patients we compared the expression in normal endocrine pancreas to the corresponding primary tumor and metastases, in two patients normal tissue to the primary tumor and in 11 patients primary tumors to the corresponding metastases. Six of ten tissues containing normal pancreas stained negative for PDGFR beta on endocrine cells, while seven of ten stained positive in the stroma. Eighteen of 21 (86%) primary tumors stained positive for PDGFR beta on tumor cells and all had positive stroma stainings. All 19 metastases stained positive for PDGFR beta on tumor cells and in evaluable stroma (n=16). We have found that PDGFR beta is more frequently expressed in primary EPTs and metastases as compared to normal endocrine pancreatic tissue. This is also true for PDGFR beta expression in the corresponding stroma. We suggest that new therapeutic options to inhibit the growth and spread of EPTs could include targeting of PDGFR beta.
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| 5. |
- Fyrsten, Ellen, et al.
(author)
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Long-Term Surveillance of Treated Hyperparathyroidism for Multiple Endocrine Neoplasia Type 1 : Recurrence or Hypoparathyroidism?
- 2016
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 40:3, s. 615-621
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Journal article (peer-reviewed)abstract
- BACKGROUND: Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is surgically treated with either a subtotal parathyroidectomy removing 3 or 3,5 glands (SPX), less than 3 glands (LSPX), or a total parathyroidectomy with autotransplantation (TPX). Previous studies with shorter follow-up have shown that LSPX and SPX are associated with recurrent HPT, and TPX with hypocalcemia and substitution therapy. We examined the situation after long-term follow-up (median 20,6 years).METHODS: Sixty-nine patients with MEN1 HPT underwent 110 operations, the first operation being 31 LSPX, 30 SPX, and 8 TPX. Thirty patients underwent reoperative surgery in median 120 months later, as completion to TPX (n = 12), completion of LSPX to SPX (n = 9), extirpation of single glands (n = 3) still resulting in LSPX, and resection of forearm grafts (n = 3). Nine patients underwent a second, and 2 a third reoperation. In 24 patients genetic testing confirmed MEN1, and in the remaining heredity and phenotype led to the diagnosis.RESULTS: TPX had higher risk for hypoparathyroidism necessitating substitution therapy, at latest follow-up 50 %, compared to SPX (16 % after 3-6 months; none at latest follow-up). Recurrent HPT was common after LSPX, leading to 24 reoperations in 17 patients. No need for substitution therapy after SPX indicated forthcoming recurrent disease. Not having hypocalcemia in the postoperative period and less radical surgery than TPX were significantly associated to risk for recurrence. Further, mutation in exon 3 in the MEN1 gene may eventually be linked to risk of recurrence.CONCLUSION: LSPX is highly associated with recurrence and TPX with continuous hypoparathyroidism, also after long-term follow-up. SPX should be the chosen method in the majority of patients with MEN1 HPT.
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| 6. |
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| 7. |
- Hellman, Per, et al.
(author)
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Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses
- 2010
-
In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 34:6, s. 1373-1379
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Journal article (peer-reviewed)abstract
- BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.
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| 8. |
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| 9. |
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| 10. |
- Hessman, Ola
(author)
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Genetic studies of endocrine abdominal tumors
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- Pancreatic endocrine tumors (PETs) occur sporadically or in the familial multiple endocrine neoplasia type 1 (MEN1) syndrome, whereas midgut carcinoids are nonfamilial, malignant endocrine tumors of the intestine. For these tumor entities morphological criteria are of limited use for prognostic prediction and selection of treatment. Genetic characterization may give additional information of clinical use and reveal pathways involved in tumor development.Molecular genetic alterations in sporadic and MEN1-associated PETs and midgut carcinoids were studied with LOH and mutational analysis. In addition, immunohistochemistry was used to clarify gene expression. Detected genetic aberrations were correlated to the disease course of individual patients.Somatic mutations of the MEN1 gene at chromosome 11q13 were detected in 1/3 of sporadic PETs. Moreover, LOH was found in 70% of the lesions. All tumors with somatic MEN1 mutations displayed loss of the remaining allele showing that the MEN1 gene is involved in development of sporadic PETs. Sporadic and MEN1 PETs were analyzed for LOH at 3p, 11q13 and 18q. A relation of LOH at 11q13 and 3p to malignancy was found for the sporadic tumors. None of the benign tumors (all of them insulinomas) had allelic loss at 3p or 11q13, versus 92 % (p<0.01) of the malignant tumors (including malignant insulinomas). 1/4 of both sporadic and MEN1 lesions displayed LOH at 18q, without altered Smad4/DPC4.Genome-wide LOH screening of MEN1 PETs revealed multiple allelic deletions without general correlation to tumor size or malignancy. All tumors displayed LOH at the MEN1 locus, and 30% on chromosomes 3, 6, 8, 10, 18 and 21. Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in most tumor cells. Chromosome 6 deletions were mainly found in lesions from patients with malignant features. A similar genome-wide LOH screening was performed on midgut carcinoids. Deletions at chromosome 18q were found in 88% of the tumors indicating a potential tumor suppressor locus.
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| 11. |
- Hessman, Ola, et al.
(author)
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High success rate of parathyroid reoperation may be achieved with improved localization diagnosis
- 2008
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 774-81; discussion 782
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery, preoperative imaging studies have been increasingly adopted. We report the use of consistently applied localization diagnosis to yield high success rates in parathyroid reoperations. METHODS: Parathyroid reoperation was performed after previous parathyroid surgery in 144 patients with nonmalignant hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients who underwent parathyroid reoperation and 14 patients who were subjected to thyroid surgery before primary parathyroid operation were investigated with sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was considered adequate, additional studies were generally not obtained. RESULTS: Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all patients with previous parathyroid surgery. In patients operated from year 2000, MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and 87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q-PTH analyses provided accurate localization or regionalization in 11 of 11 recently selected patients. Q-PTH analyses in fine-needle aspirations verified parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide when operations could be terminated. In patients subjected to the algorithm of imaging procedures, reversal of hypercalcemia and apparent cure was obtained after the reoperation in 45 of 46 patients with previous parathyroid surgery, implying a success rate of 98%, and in all patients with previous thyroid surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can be improved by consistently applied sensitive methods of preoperative imaging, and reoperative procedures may then achieve nearly the same success rates as primary operations.
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| 12. |
- Hessman, Ola, et al.
(author)
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Multiple allelic deletions and intratumoral genetic heterogeneity in MEN1 pancreatic tumors
- 2001
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 86:3, s. 1355-1361
-
Journal article (peer-reviewed)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple tumors of the endocrine pancreas, the parathyroid, the pituitary, and other tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1 tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of 23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1 patients. Multiple allelic deletions were found. Fractional allelic loss varied from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11, whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over 30%. Different lesions from individual patients had discrepant patterns of LOH. Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in most tumor cells, whereas other chromosomal loci were deleted in portions of the analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients with malignant features. Fractional allelic loss did not correlate to malignancy or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to maintain DNA integrity and demonstrate signs of chromosomal instability.
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| 13. |
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| 14. |
- Hessman, Ola, et al.
(author)
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Mutation of the Multiple Endocrine Neoplasia Type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas
- 1998
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 58:3, s. 377-379
-
Journal article (peer-reviewed)abstract
- Endocrine pancreatic tumors are rare neoplasms that occur sporadically or as part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. Germ-line mutations of the MEN1 gene, located at 11q13, have been demonstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 together with somatic MEN1 mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on 11q13 was found in 70% of the tumors. Three tumors displayed somatic mutations of the MEN1 gene together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.
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| 15. |
- Hessman, Ola, et al.
(author)
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Randomized clinical trial comparing open with video-assisted minimally invasive parathyroid surgery for primary hyperparathyroidism
- 2010
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 97:2, s. 177-184
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies of video-assisted techniques for parathyroidectomy in patients with primary hyperparathyroidism have found similar or better results compared with bilateral neck exploration. The aim of the present study was to compare open minimally invasive parathyroidectomy with the video-assisted technique for primary hyperparathyroidism in a multicentre randomized trial. METHODS: Some 143 patients were randomized to open (n = 75) or video-assisted (n = 68) parathyroidectomy after positive sestamibi scintigraphy. There were no differences in preoperative data. The open operation was performed through a 15-mm incision. The video-assisted techniques used were minimally invasive video-assisted parathyroidectomy (MIVAP) or video-assisted parathyroidectomy using the lateral approach (VAPLA). Data were collected prospectively including postoperative pain scoring. RESULTS: The procedure was significantly quicker for the open compared to the video assisted operations: mean(s.d.) 60(35) versus 84(47) min (P = 0.001). Both groups of patients had similar conversion rates and the same outcome, with comparable incision lengths, low scores for postoperative neck discomfort, high cosmetic satisfaction and low complication rates. CONCLUSION: Open minimally invasive parathyroidectomy for primary hyperparathyroidism was quicker than either video-assisted technique.
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| 16. |
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| 17. |
- Lindberg, Daniel, et al.
(author)
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Cyclin-dependent kinase 4 (CDK4) expression in pancreatic endocrine tumors
- 2007
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 86:2, s. 112-118
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Journal article (peer-reviewed)abstract
- Background/Aims: Pancreatic endocrine tumors (PETs) occur sporadically, in association with the multiple endocrine neoplasia type 1 (MEN1) and the von Hippel-Lindau syndromes. CDK4 is central to the cell cycle control in pancreatic cells, and we have assessed whether CDK4 expression is deregulated in 18 human sporadic or familial PETs. Methods: Real-time quantitative PCR, immunohistochemistry, DNA sequencing, and Western blot analysis were used. Results: CDK4 mRNA was expressed in all PETs within the range of the arbitrary control. CDK4 protein was absent in normal pancreatic islets but distinctly expressed in all PETs as determined by immunohistochemistry. CDK4 expression was confirmed by Western blot analysis. No significant differences of CDK4 expression were observed between the groups of benign and malignant PETs or between tumors with or without MEN1 gene mutations. CDK4 expression was not due to gene amplification, and no mutations were identified in coding exons and RNA splice sites. c-Myc is known to be overexpressed in PETs and directly augments CDK4 expression in other cell types. Analysis of consecutive tissue sections for CDK4 and c-Myc showed overlapping homo- or heterogeneous immunostaining in all 18 PETs. Conclusion: We conclude that CDK4 and c-Myc is generally expressed in benign and malignant PETs, and regardless of MEN1 mutation-al status. Targeting of CDK4 may present an alternative to traditional chemotherapy of PETs in the future.
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| 18. |
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| 19. |
- Lundstam, Karolina, et al.
(author)
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Effect of Surgery Versus Observation : Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study)
- 2017
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 32:9, s. 1907-1914
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Journal article (peer-reviewed)abstract
- Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm(2) and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p<0.001) and CTX-1 (p<0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm(2)) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p<0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p<0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm(2)) for all compartments (FN, p<0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p<0.001) with the exception of the LS, whereBMDwas stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT.
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| 20. |
- Lundstam, Karolina, et al.
(author)
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Effects of parathyroidectomy versus observation on the development of vertebral fractures in mild primary hyperparathyroidism
- 2015
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1359-1367
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Journal article (peer-reviewed)abstract
- Context: Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. Objective: To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. Design: Prospective, randomized controlled study (SIPH study), 5-year follow-up. Setting: Multicenter, tertiary referral centers. Patients: Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, mean age at inclusion 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). Intervention: Parathyroidectomy vs observation. Main outcome measures: Biochemistry, BMD and new radiographic vertebral fractures. Results: Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P<0.02). After surgery, BMD Z-scores increased significantly in both compartments (P<0.02 for both), with a highly significant treatment effect of surgery compared to observation (P<0.001). During follow-up, 5 new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P=0.058). Conclusion: Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.
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| 21. |
- Lundstam, Karolina, et al.
(author)
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Positive Effect of Parathyroidectomy Compared to Observation on BMD in a Randomized Controlled Trial of Mild Primary Hyperparathyroidism
- 2023
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:3, s. 372-380
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Journal article (peer-reviewed)abstract
- Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years to the end of study (EOS). BMD was measured with dual-energy X-ray absorptiometry (DXA), peripheral fractures were noted, and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD compared with OBS for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (p < 0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33, and ultradistal radius (UDR) (p < 0.001). Even though there was a significant treatment effect of PTX compared with OBS, there was only a significant increase in BMD over time for LS (p < 0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention-to-treat (mITT) analysis nor per protocol analysis. Because BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective.(c) 2023 The Authors.
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| 22. |
- Norlén, Olov, et al.
(author)
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Long-Term Results of Surgery for Small Intestinal Neuroendocrine Tumors at a Tertiary Referral Center
- 2012
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 36:6, s. 1419-1431
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Journal article (peer-reviewed)abstract
- BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients. MATERIAL AND METHODS: We included 603 consecutive patients (325 men; age at diagnosis 63 ± 11 years [mean ± SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra-abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery. RESULTS: Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205). CONCLUSIONS: For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.
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| 23. |
- Norlén, Olov, et al.
(author)
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Prophylactic Cholecystectomy in Midgut Carcinoid Patients
- 2010
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 34:6, s. 1361-1367
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Journal article (peer-reviewed)abstract
- Patients with midgut carcinoid (MGC) tumors are commonly treated with somatostatin analogs. Adverse effects of these drugs include impairment of gallbladder function, formation of gallstones, and cholecystitis. Prophylactic cholecystectomy has been advocated, but data to support this recommendation are sparse. We have analyzed a cohort of 235 patients with MGC focusing on the risk for gallstone formation and complications thereof. Forty-eight of the 235 patients had been cholecystectomized before surgery for MGC. Of the remaining 187 patients, 144 were treated with somatostatin analogs. Eighteen of the 187 patients had their gall bladder removed during the primary carcinoid surgery. Twenty-two of the 144 somatostatin-analog-treated patients developed complications, such as gallbladder empyema (n = 1), cholangitis (n = 2), acute cholecystitis (n = 6), acute pancreatitis (n = 1) or acute pancreatitis and cholecystitis (n = 1), or biliary colic (n = 11). Ninety-two of the 144 were examined during surgery, by computed tomography, or by ultrasound, most for reasons other than gallbladder-related indications, and 63% (58/92) of these examinations revealed gallstones. Of the 43 patients not treated with somatostatin analogs, only 3 patients suffered from biliary colic and underwent cholecystectomy. In our study the incidence of gallstone-related complications seems to be higher than in the general population. We recommend that prophylactic cholecystectomy is liberally performed during laparotomy for MGC if patients are planned to undergo treatment with somatostatin analogs.
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| 24. |
- Pretorius, Mikkel, et al.
(author)
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Mortality and Morbidity in Mild Primary Hyperparathyroidism : Results From a 10-Year Prospective Randomized Controlled Trial of Versus Observation
- 2022
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In: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 175:6, s. 812-
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Journal article (peer-reviewed)abstract
- Background: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. Objective: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). Design: Prospective randomized controlled trial. (ClinicalTrials. gov: NCT00522028) Setting: Eight Scandinavian referral centers. Patients: From 1998 to 2005, 191 patients with mild PHPT were included. Intervention: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). Measurements: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. Results: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). Limitation: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. Conclusion: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. Primary Funding Source: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority
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| 25. |
- Salem, F. A., et al.
(author)
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A Nested Case-Control Study on the Risk of Surgical Site Infection After Thyroid Surgery
- 2018
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In: World Journal of Surgery. - : SPRINGER. - 0364-2313 .- 1432-2323. ; 42:8, s. 2454-2461
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Journal article (peer-reviewed)abstract
- It is unclear if antibiotic prophylaxis reduces the risk of surgical site infection (SSI) in thyroid surgery. This study assessed risk factors for SSI and antibiotic prophylaxis in subgroups of patients. A nested case-control study on patients registered in the Swedish National Register for Endocrine Surgery was performed. Patients with SSI were matched 1:1 by age and gender to controls. Additional information on patients with SSI and controls was queried from attending surgeons using a questionnaire. Risk factors for SSI were evaluated by logistic regression analysis and presented as odds ratio (OR) with 95% confidence interval (CI). There were 9494 operations; 109 (1.2%) patients had SSI. Patients with SSI were older (median 53 vs. 49 years) than patients without SSI p = 0.01 and more often had a cancer diagnosis 23 (21.1%) versus 1137 (12.1%) p = 0.01. In the analysis of patients with SSI versus controls, patients with SSI more often had post-operative drainage 68 (62.4%) versus 46 (42.2%) p = 0.01 and lymph node surgery 40 (36.7%) versus 14 (13.0%) p < 0.01, and both were independent risk factors for SSI, drain OR 1.82 (CI 1.04-3.18) and lymph node dissection, OR 3.22 (95% CI 1.32-7.82). A higher number of 26(62%) patients with independent risk factors for SSI and diagnosed with SSI did not receive antibiotic prophylaxis. Data were missing for 8 (31%) patients. Lymph node dissection and drain are independent risk factors for SSI after thyroidectomy. Antibiotic prophylaxis might be considered in patients with these risk factors.
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| 26. |
- Salem, Farhad Allahyar, et al.
(author)
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Evaluating risk factors for re-exploration due to postoperative neck hematoma after thyroid surgery: a nested case-control study.
- 2019
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In: Langenbeck's archives of surgery. - : Springer Science and Business Media LLC. - 1435-2451 .- 1435-2443. ; 404:7, s. 815-823
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Journal article (peer-reviewed)abstract
- Postoperative bleeding after thyroid surgery remains a potentially lethal complication. Outpatient thyroidectomy is an increasing trend in the high volume centers. There is a need to identify risk factors for postoperative bleeding in order to select proper patients for outpatient thyroidectomy. This study aimed to investigate this issue using a national population-based register.A nested case-control study on patients registered in the Swedish national register for endocrine surgery (SQRTPA) was performed. Patients with postoperative bleeding were matched 1:1 by age and gender to controls. Additional information on cases and controls was obtained from attending surgeons using a questionnaire. Risk factors for postoperative bleeding were evaluated with logistic regression and are presented as odds ratios (ORs) with 95% confidence intervals (CIs). The time of bleeding in relation to surgery was also investigated.There were 9494 operations, and 174 (1.8%) of them involved postoperative bleeding. In the whole cohort, patients with postoperative bleeding were older, 58 (46-69) vs. 49 (37-62) years, than patients without, p<0.01. Male patients had a higher risk of bleeding, OR 2.18 (95% CI 1.58-2.99). In the case-control cohort, drain was an independent risk factor for bleeding, OR 1.64 (1.05-2.57). Two-thirds of patients bled within 6h after surgery. The incidence of bleeding after 24h was 10%.High age, male gender, and drain are independent risk factors for bleeding after thyroid surgery. Even with careful patient selection, prolonged observation might be necessary in thyroid surgery.
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| 27. |
- Sandgren, Johanna, 1979-
(author)
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Array-based Genomic and Epigenomic Studies in Healthy Individuals and Endocrine Tumours
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The human genome is a dynamic structure, recently recognized to present with significant large-scale structural variation. DNA-copy number changes represent one common type of such variation and is found both between individuals and within the somatic cells of the same individual, especially in disease states like cancer. Apart from DNA-rearrangements, epigenomic changes are increasingly acknowledged as important events in the maintenance of genomic integrity. In this thesis, different array-based methods have been applied for global genomic and epigenomic profiling of both normal and cancer cells. In paper I, a genomic microarray was established and used to determine DNA-copy number variants (CNVs) in a cohort of 76 healthy individuals from three ethnic populations. We identified 315 CNV regions that in total encompassed ~3,5% of the genome. In paper II, the array was utilized to discover CNVs within several differentiated tissues from the same subject. Six variants were identified providing evidence for somatic mosaicism. In paper III and IV we studied pheochromocytomas and paragangliomas, rare endocrine tumours that most often present as benign and sporadic with unclear genetic/epigenetic cause. Genome-wide DNA-copy number analysis of 53 benign and malignant samples in paper III revealed numerous common and novel chromosomal regions of losses and gains. High frequencies of relatively small overlapping regions of deletions were detected on chromosome 1p arm, encompassing several candidate tumour suppressor genes. In paper IV, an epigenomic map for two histone modifications associated with silent (H3K27me3) or active (H3K4me3) gene transcription, was generated for one malignant pheochromocytoma. Integrated analysis of global histone methylation, copy number alterations and gene expression data aided in the identification of candidate tumour genes. In conclusion, the performed studies have contributed to gain knowledge of CNVs in healthy individuals, and identified regions and genes which are likely associated with the development and progression of pheochromocytoma/paraganglioma.
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| 28. |
- Sandgren, Johanna, et al.
(author)
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Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis
- 2010
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In: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:3, s. 561-579
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Journal article (peer-reviewed)abstract
- Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (> or = 32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (> or = 14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
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| 29. |
- Segersten, Ulrika, et al.
(author)
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25-hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-hydroxylated vitamin D analogue
- 2005
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7, s. R980-R986
-
Journal article (peer-reviewed)abstract
- INTRODUCTION:The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.METHODS:The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.RESULTS:1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3.CONCLUSION:These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed.
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| 30. |
- Stålberg, Peter, et al.
(author)
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Surgical treatment of Graves' disease : evidence-based approach.
- 2008
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:7, s. 1269-77
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Journal article (peer-reviewed)abstract
- BACKGROUND: The optimal treatment of Graves disease (GD) is still controversial. Surgery is one treatment option along with radioactive iodine (RAI) and antithyroid medication. In this evidence-based review, we examine four issues: (1) Is surgery better than RAI or long-term antithyroid medication? (2) What is the recommended surgical approach? (3) How does the presence of Graves' ophthalmopathy (GO) influence the role of surgery? (4) What is the role of surgery in children with GD? METHODS: We conducted a systematic review of the literature using evidence-based criteria regarding these four issues. RESULTS: (1) There are no recommendations reaching any grade of evidence for which treatment to choose for adults with GD. (2) Total thyroidectomy has complication rates equal to those seen with lesser resections but it has higher cure rates and negligible recurrence rates (Level I-IV data leading to a grade A recommendation). (3) Data support surgery when severe GO is present, but RAI combined with glucocorticoids may be equally safe (Level II-IV data, grade B recommendation). The extent of thyroid resection does not influence the outcome of GO (Level II data, grade B recommendation). (4) Based on the available data, definitive treatment can be advocated for children (Level IV data, grade C recommendation) using either RAI or surgery. No recommendation can be given as to whether RAI or surgery is preferred owing to the lack of studies addressing this issue. Increased cancer risk with RAI in children below the age of 5 years supports surgery in this setting (Level I data, grade A recommendation). CONCLUSION: If surgery is considered for definitive management, evidence-based criteria support total thyroidectomy as the surgical technique of choice for GD. Available evidence also supports surgery in the presence of severe endocrine GO. Children with GD should be treated with an ablative strategy. Whether this is achieved by total thyroidectomy or RAI may still be debatable. Data on long-term cancer risk are missing or conflicting; and until RAI has proven harmless in children, we continue to recommend surgery in this group.
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| 31. |
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| 32. |
- Åkerström, Göran, et al.
(author)
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Carcinoid tumors
- 2004
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In: A Companion to Specialist Surgical Practice. - : Elsevier Ltd Edinburgh.
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Book chapter (other academic/artistic)
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| 33. |
- Åkerström, Göran, et al.
(author)
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Gastrointestinal carcinoids
- 2009
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In: Endocrine surgery. - London : Saunders. - 9780702030161 ; , s. 163-169
-
Book chapter (pop. science, debate, etc.)
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| 34. |
- Åkerström, Göran, et al.
(author)
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Gastrointestinal carcinoids
- 2005
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In: Endocrine Surgery. - : Elsevier Ltd Edinburgh. ; , s. 163-197
-
Book chapter (other academic/artistic)
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Åkerström, Göran, et al.
(author)
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Remedial Parathyroid Surgery
- 2012. - 2
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In: <em>Surgery of the Thyroid and Parathyroid Gland</em>s. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642234583 ; , s. 555-577
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Book chapter (peer-reviewed)
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| 40. |
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| 41. |
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