SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Crona Joakim) ;pers:(Norlén Olov)"

Sökning: WFRF:(Crona Joakim) > Norlén Olov

  • Resultat 1-10 av 12
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Backman, Samuel, et al. (författare)
  • Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
  • 2017
  • Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:2, s. 705-712
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
  •  
2.
  • Botling, Johan, et al. (författare)
  • High-grade progression confers poor survival in pancreatic neuroendocrine tumors
  • 2020
  • Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:11-12, s. 891-898
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes PanNET differentiation and proliferation over time, and to correlate findings to overall survival (OS).PATIENTS AND METHODS: In this retrospective cohort study we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were re-evaluated with regard to tumor histopathology and Ki-67 index.RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1-38%), grade 1 n=8, grade 2 n=36, and grade 3 n=2. The median change in Ki-67 index (absolute value; follow-up - baseline) was +14% (range -11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n=24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (HR 3.89, 95% CI 1.91-7.94, P<0.001).CONCLUSIONS: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.
  •  
3.
  • Crona, Joakim, et al. (författare)
  • Metastases from Neuroendocrine Tumors to the Breast Are More Common than Previously Thought. A Diagnostic Pitfall?
  • 2013
  • Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 37:7, s. 1701-1706
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastases from neuroendocrine tumors (NETs) to the breast have been described as a rare phenomenon. Presentation, imaging results, and cytopathologic findings of these tumours may closely mimic those of a mammary carcinoma. This study was a retrospective review of 661 patients with metastatic NETs, of whom 280 were females, treated at Uppsala University Hospital, Uppsala, Sweden. Patients with pathological breast lesions were identified. Histopathological slides from available NET breast lesions were analyzed for mammary carcinoma and neuroendocrine markers. We have identified 20 female patients with NET metastases to the breast, 11/235 with small intestinal NETs, 8/55 with lung NETs, and 1/6 with thymic NETs. There were no male patients with NET metastatic to the breast. Four patients had their breast lesion initially diagnosed as mammary carcinoma. Retrospectively, these lesions showed negative staining for mammary carcinoma markers. Metastases to the breast from neuroendocrine tumors may be more common than previously thought. Patients with a lesion to the breast and symptoms typical for NET may benefit from additional histopathological investigation, because NET metastases and mammary carcinoma have different immunohistochemical profiles.
  •  
4.
  •  
5.
  • Crona, Joakim, et al. (författare)
  • Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours
  • 2016
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:2, s. 445-452
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT:As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage.OBJECTIVES:The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients.DESIGN, SETTING, AND PARTICIPANTS:This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail.RESULTS:In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P < .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively.CONCLUSION:Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course.
  •  
6.
  • Crona, Joakim, et al. (författare)
  • Somatic Mutations and Genetic Heterogeneity at the CDKN1B Locus in Small Intestinal Neuroendocrine Tumors
  • 2015
  • Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 22, s. 1428-1435
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Until recently, the genetic landscape of small intestinal neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations, most commonly a loss on chromosome 18. Intertumor heterogeneity with nonconcordant genotype in paired primary and metastatic lesions also is described, further contributing to the difficulty of unraveling the genetic enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B (p27) as a haploinsufficient tumor suppressor gene.METHODS: This study aimed to determine the frequency of CDKN1B inactivation and to investigate genotype-phenotype correlations. It investigated 362 tumors from 200 patients. All samples were resequenced for mutations in CDKN1B using automated Sanger sequencing. The expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors.RESULTS: Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in CDKN1B including 13 insertion deletions, four nonsense variants, and one stop-loss variant. All variants with available nontumoral DNA were classified as somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected respectively in six of ten and two of ten patients. Patients with CDKN1B mutated tumors had both heterogeneous disease presentation and diverse prognosis. Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found.CONCLUSION: This study corroborates the finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene characterized by inter- and intratumor heterogeneity in SI-NETs.
  •  
7.
  • Kjaer, Josefin, et al. (författare)
  • Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors : A Propensity-Score Matched Cohort Study
  • 2022
  • Ingår i: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study.Background: Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results.Methods: Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women’s Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000–2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival.Results: Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043).Conclusions: Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.
  •  
8.
  • Kjaer, Josefin, et al. (författare)
  • Long-term outcome after resection and thermal hepatic ablation of pancreatic neuroendocrine tumour liver metastases
  • 2021
  • Ingår i: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Pancreatic neuroendocrine tumours (Pan-NETs) are rare tumours that often present with or develop liver metastases. The aim of this retrospective study was to evaluate liver surgery and thermal hepatic ablation (THA) of Pan-NET liver metastases and to compare the outcomes with those of a control group. METHOD: Patients with Pan-NET treated in Uppsala University Hospital and Sahlgrenska University Hospital from 1995-2018 were included. Patient records were scrutinized for baseline parameters, survival, treatment and complications. RESULTS: Some 108 patients met the criteria for inclusion; 57 patients underwent treatment with liver surgery or THA and 51 constitute the control group. Median follow-up was 3.93 years. Five-year survival in the liver surgery/THA group was 70.6 (95 per cent c.i. 0.57 to 0.84) per cent versus 42.4 (95 per cent c.i. 40.7 to 59.1) per cent in the control group (P = 0.016) and median survival was 9.1 (95 per cent c.i. 6.5 to 11.7) versus 4.3  (95 per cent c.i. 3.4-5.2) years. In a multivariable analysis, surgery or THA was associated with a decreased death-years rate (hazard ratio 0.403 (95 per cent c.i. 0.208 to 0.782, P = 0.007). CONCLUSION: Liver surgery and/or THA was associated with longer overall survival in Pan-NET with acceptable mortality and morbidity rates. These treatments should thus be considered in Pan-NET patients with reasonable tumour burden in an intent to alleviate symptoms and to improve survival.
  •  
9.
  • Kjaer, Josefine, et al. (författare)
  • Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation
  • 2023
  • Ingår i: World Journal of Surgery. - : Springer Nature. - 0364-2313 .- 1432-2323. ; 47, s. 340-347
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The use of liver transplantation (LT) in patients with stage IV neuroendocrine pancreatic tumors (pan-NET) is under debate. Previous studies report a 5-year survival of 27-53% after LT in pan-NET and up to 92.7% in patients with mixed NETs. This study aimed to determine survival rates of patients with stage IV pan-NET meeting criteria for LT while only subjected to multimodal treatment.METHODS: Medical records of patients with pan-NET diagnosed from 2000 to 2021 at a tertiary referral center were evaluated for eligibility. Patients without liver metastases, who did not undergo primary tumor surgery, age > 75 years and with grade 3 tumors were excluded. The patients were divided into groups; all included patients, patients meeting the Milan, the United Network for Organ Sharing (UNOS) or the European Neuroendocrine Tumor Society (ENETS) criteria for LT. Kaplan-Meier survival analysis was used to calculate overall survival.RESULTS: Out of 519 patients with pan-NET, 41 patients were included. Mean follow-up time was 5.4 years. Overall survival was 9.3 years (95% Cl 6.8-11.7), and 5-year survival was 64.7% (95% CI 48.2-81.2). Patients meeting the Milan, ENETS and UNOS criteria for LT had a 5-year survival of 64.9% (95% CI 32.2-97.6), 85.7% (95% CI 59.8-100.0) and 55.4% (95% CI 26.0-84.8), respectively.CONCLUSIONS: In patients with stage IV pan-NET, grade 1 and 2, with no extra abdominal disease, 5-year survival was 64.7% (95% CI 48.2-81.2). As these survival rates exceed previously published series of LT for pan-NET, the evidence base for this treatment is very weak.
  •  
10.
  • Vyakaranam, Achyut Ram, et al. (författare)
  • C-11-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma
  • 2019
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing C-11-hydroxy-ephedrine (C-11-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. C-11-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of C-11-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor C-11-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R-2 = 0.22, p = 0.016). C-11-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor C-11-HED uptake were not helpful for tumor characterization.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 12

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy