| 1. |
|
|
| 2. |
|
|
| 3. |
- Alexandraki, Krystallenia I., et al.
(författare)
-
The effect of prophylactic surgery in survival and HRQoL in appendiceal NEN
- 2020
-
Ingår i: Endocrine. - : Springer. - 1355-008X .- 1559-0100. ; 70:1, s. 178-186
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL).METHODS: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis' validation.RESULTS: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08-1] vs 0.83[0.4-1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group.CONCLUSIONS: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.
|
|
| 4. |
- Ali, A., et al.
(författare)
-
Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells
- 2022
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 76, s. 543-557
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Metformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous. Methods: MF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency. Results: MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1α proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity. Conclusions: These findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.
|
|
| 5. |
|
|
| 6. |
- Apelqvist, Jan
(författare)
-
Diagnostics and treatment of the diabetic foot.
- 2012
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 41:3, s. 384-397
-
Tidskriftsartikel (refereegranskat)abstract
- Every 30 s, a lower limb is amputated due to diabetes. Of all amputations in diabetic patients 85% are preceded by a foot ulcer which subsequently deteriorates to a severe infection or gangrene. There is a complexity of factors related to healing of foot ulcers including strategies for treatment of decreased perfusion, oedema, pain, infection, metabolic disturbances, malnutrition, non-weight bearing, wound treatment, foot surgery, and management of intercurrent disease. Patients with diabetic foot ulcer and decreased perfusion do often not have rest pain or claudication and as a consequence non-invasive vascular testing is recommended for early recognition of ulcers in need of revascularisation to achieve healing. A diabetic foot infection is a potentially limb-threatening condition. Infection is diagnosed by the presence or increased rate of signs inflammation. Often these signs are less marked than expected. Imaging studies can diagnose or better define deep, soft tissue purulent collections and are frequently needed to detect pathological findings in bone. The initial antimicrobial treatment as well as duration of treatment is empiric. There is a substantial delay in wound healing in diabetic foot ulcer which has been related to various abnormalities. Several new treatments related to these abnormalities have been explored in wound healing with various successes. An essential part of the strategy to achieve healing is an effective offloading. Many interventions with advanced wound management have failed due to not recognizing the need for effective offloading. A multidisciplinary approach to wounds and foot ulcer has been successfully implemented in different centres with a substantial decrease in amputation rate.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Borghammar, Camilla, et al.
(författare)
-
Non-functioning pituitary microadenoma in children and adolescents : Is follow-up with diagnostic imaging necessary?
- 2023
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 79, s. 152-160
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements.METHODS: The children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated.RESULTS: In total, 74 children, median age 12 years (range 3-17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2-7) with a median follow-up of 37 months (range 4-189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression.CONCLUSION: Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4-6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.
|
|
| 10. |
|
|
| 11. |
- Brue, Thierry, et al.
(författare)
-
Diabetes in patients with acromegaly treated with pegvisomant : observations from acrostudy
- 2019
-
Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 63:3, s. 563-572
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeTo explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study.MethodsPatients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4-5yrs of PEGV treatment.ResultsAmong 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.058.7mg/dl at baseline, 116.4 +/- 44.8mg/dl at year 1 and 120.0 +/- 44.3mg/dl at yr 4. Mean HbA1c was 6.6 +/- 1.2 % at yr 1 vs. 7.0 +/- 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n=109), mean blood glucose decreased by 20.2mg/dl at yr 4, mean HbA1c was 7.0 +/- 1.5% at baseline vs. 6.8 +/- 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs.Conclusions p id=Par4 Patients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Calissendorff, Jan, et al.
(författare)
-
68Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors
- 2014
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 47:1, s. 169-176
-
Tidskriftsartikel (refereegranskat)abstract
- Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by 68Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All 68Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients’ activity of daily life. 68Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of 68Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.
|
|
| 15. |
- Calissendorff, Jan, et al.
(författare)
-
Ileal neuroendocrine tumors and heart : not only valvular consequences
- 2015
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 48:3, s. 743-755
-
Forskningsöversikt (refereegranskat)abstract
- Ileal neuroendocrine tumors (NETs) often progress slowly, but because of their generally nonspecific symptoms, they have often metastasized to local lymph nodes and to the liver by the time the patient presents. Biochemically, most of these patients have increased levels of whole blood serotonin, urinary 5-hydroxyindoleacetic acid, and chromogranin A. Imaging work-up generally comprises computed tomography or magnetic resonance imaging and somatostatin receptor scintigraphy, or in recent years positron emission tomography with Ga-68-labeled somatostatin analogs, allowing for detection of even sub-cm lesions. Carcinoid heart disease with affected leaflets, mainly to the right side of the heart, is a well-known complication and patients routinely undergo echocardiography to diagnose and monitor this. Multitasking surgery is currently recognized as first-line treatment for ileal NETs with metastases and carcinoid heart disease. Open heart surgery and valve replacement are advocated in patients with valvular disease and progressive heart failure. When valvulopathy in the tricuspid valve results in right-sided heart failure, a sequential approach, performing valve replacement first before intra-abdominal tumor-reductive procedures are conducted, reduces the risk of bleeding. Metastases to the myocardium from ileal NETs are seen in <1-4.3% of patients, depending partly on the imaging technique used, and are generally discovered in those affected with widespread disease. Systemic treatment with somatostatin analogs, and sometimes alpha interferon, is first-line medical therapy in metastatic disease to relieve hormonal symptoms and stabilize the tumor. This treatment is also indicated when heart metastases are detected, with the addition of diuretics and fluid restriction in cases of heart failure. Myocardial metastases are rarely treated by surgical resection.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Dahlqvist, Per, et al.
(författare)
-
Testicular enlargement in a patient with a FSH-secreting pituitary adenoma
- 2010
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 37:2, s. 289-293
-
Tidskriftsartikel (refereegranskat)abstract
- Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.
|
|
| 22. |
- Daskalakis, Kosmas, et al.
(författare)
-
Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms
- 2019
-
Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 64:2, s. 384-392
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.Design: This is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.Methods: Twenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.Results: The prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P=0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P=0.001 and P<0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P=0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P=0.12).Conclusion: EPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.
|
|
| 23. |
- Daskalakis, Kosmas, 1979-, et al.
(författare)
-
Increased autophagy/mitophagy levels in primary tumours of patients with pancreatic neuroendocrine neoplasms
- 2020
-
Ingår i: Endocrine. - : Springer. - 1355-008X .- 1559-0100. ; 68:2, s. 438-447
-
Tidskriftsartikel (refereegranskat)abstract
- Background/aims: We assessed the levels of autophagy and mitophagy, that are linked to cancer development and drug resistance, in well differentiated pancreatic neuroendocrine neoplasms (PanNENs) and correlated them with clinico-pathological parameters.Methods: Fluorescent immunostaining for the autophagy markers LC3 Beta and p62/or LAMP1 was performed on 22 PanNENs and 11 controls of normal pancreatic tissues and validated through Western blotting. Autophagy quantitative scoring was generated for LC3B-positive puncta and analysed in relation to clinico-pathological parameters. TOMM20/LC3B qualitative assessment of mitophagy levels was undertaken by fluorescent immunostaining. The presence of autophagy/mitophagy was validated by transmission electron microscopy.Results: Autophagy levels (LC3B-positive puncta/cell) were discriminative for normal vs. NEN pancreatic tissue (p = 0.007). A significant association was observed between autophagy levels and tumour grade (Ki67 < 3% vs. Ki67 >= 3%; p = 0.021), but not functionality (p = 0.266) size (cut-off of 20 mm; p = 0.808), local invasion (p = 0.481), lymph node- (p = 0.849) and distant metastases (p = 0.699). Qualitative assessment of TOMM20/LC3B demonstrated strong mitophagy levels in PanNENs by fluorescent immunostaining as compared with normal tissue. Transmission electron microscopy revealed enhanced autophagy and mitophagy in PanNEN tissue. Response to molecular targeted therapies in metastatic cases (n = 4) did not reveal any patterns of association to autophagy levels.Conclusions: Increased autophagy levels are present in primary tumours of patients with PanNENs and are partially attributed to upregulated mitophagy. Grade was the only clinico-pathological parameter associated with autophagy scores.
|
|
| 24. |
- Daskalakis, Kosmas, et al.
(författare)
-
The risk of lymph node metastases and their impact on survival in patients with appendiceal neuroendocrine neoplasms : a systematic review and meta-analysis of adult and paediatric patients
- 2020
-
Ingår i: Endocrine. - : Springer. - 1355-008X .- 1559-0100. ; 67:1, s. 20-34
-
Forskningsöversikt (refereegranskat)abstract
- Background There are no clear histopathological parameters determining the risk of lymph node (LN) metastases and appropriateness of completion prophylactic right hemicolectomy (RHC) in patients with appendiceal neuroendocrine neoplasms (ANENs). Materials and methods The PubMed, Cochrane Library, Embase, Web of Science and SCOPUS databases were searched up to November 2018. Quality/risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results A total of 526 articles were screened. In 11 adult and 3 paediatric studies, 602 and 77 unique patients, respectively, with ANEN and undergoing RHC, were included. The rate of LN metastases for a cutoff size >10 mm was 48.6% (vs 12.1% for lesions <10 mm) among adult patients, with an odds ratio (OR) of 4.8 (95% CI, 1.5-15.8). For 20 mm size cutoff, these figures were 61% (vs 28.2% for lesions <20 mm) with an OR of 3.2 (95% CI, 1.3-7.8). Vascular-, lymph vessel- and perineural invasions were identified as predictive factors for LN metastases in adult patients. In paediatric patients, there were no strong morphological predictors for LN metastases. The 10-year disease-specific survival (DSS) for adult patients without LN metastases was 99.2% vs 95.6% in patients with LN (OR: 0.2; 95% CI, 0.02-2.4). The complication rate of prophylactic RHC was 11.4%. Conclusions This meta-analysis demonstrates that tumour size >20 mm as well as >10 mm and/or vascular-, lymph vessel- and perineural invasions are associated with increased risk for LN metastases in adult patients with ANEN. The prognostic value of LN positivity remains to be determined in further studies with long-term follow-up.
|
|
| 25. |
|
|
