| 11. |
|
|
| 12. |
- Kjaer, Josefin, et al.
(author)
-
Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors : A Propensity-Score Matched Cohort Study
- 2022
-
In: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 3:1
-
Journal article (peer-reviewed)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.
|
|
| 13. |
- Kjaer, Josefin, et al.
(author)
-
Long-term outcome after resection and thermal hepatic ablation of pancreatic neuroendocrine tumour liver metastases
- 2021
-
In: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:4
-
Journal article (peer-reviewed)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 3.93years. 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.
|
|
| 14. |
- Kjaer, Josefine, et al.
(author)
-
Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation
- 2023
-
In: World Journal of Surgery. - : Springer Nature. - 0364-2313 .- 1432-2323. ; 47, s. 340-347
-
Journal article (peer-reviewed)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.
|
|
| 15. |
- Kjaer, Josefine, 1985-
(author)
-
Pancreatic Neuroendocrine Tumors : Surgical Treatment and Follow-up
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Pancreatic neuroendocrine tumors (Pan-NET), are rare, heterogenous and derive from the hormone producing cells in the pancreas. The functioning tumors that overproduce hormones cause clinical syndromes with specific symptoms due to the hormonal production. However, the majority of patients have non-functioning tumors, and in lack of symptoms, these more often present with, or develop, liver metastases. This thesis focuses on treatment of metastasized pan-NET, stage IV, from a surgical perspective. As some patients operated on for localized disease eventually experience recurrence, it would also be beneficial to be able to predict which patients that are at a higher risk for recurrence. In paper I, outcome after primary tumor resection in pan-NET patients, stage IV, was evaluated. An association between primary tumor resection and prolonged survival was found in patients, both before and after propensity score match. In paper II, outcome after hepatic resection and thermal hepatic ablation of liver metastases, in patients previously subjected to primary tumor resection, was scrutinized. Survival rates were significantly higher in the hepatic resection/thermal hepatic ablation group, and in a multivariable analysis, hepatic resection/thermal hepatic ablation remained a significant positive prognostic factor for prolonged survival. In paper III, patients with unresectable liver metastases, eligible for liver transplantation were investigated. A very small group of all pan-NET stage IV patients was eligible for liver transplantation and even fewer patients met any of the current selection criteria for liver transplantation. The survival rates for these patients, only subjected to multimodal treatment, were comparable to the survival rates after liver transplantation, presented in previously published studies. In paper IV, an external validation of a prediction model for recurrence after resection of non-metastatic, non-functioning, grade 1-2 tumors, was performed. The model performed well in the validation and is available online.To conclude, both primary tumor resection and surgical and ablative treatment of liver metastases in stage IV pan-NET, were associated with prolonged survival in analyses controlling for bias and possible confounders. However, the evidence base to perform liver transplantation in patients with pan-NET is weak. A prediction model for recurrence after radical surgery of non-metastatic pan-NET was externally validated with success. Our findings provide additional knowledge regarding treatment of stage IV pan-NET and could also help us predict which patients that will recur after surgery.
|
|
| 16. |
- Lase, Ieva, et al.
(author)
-
Adrenalectomy in ectopic Cushing's syndrome : A retrospective cohort study from a tertiary care centre
- 2021
-
In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 33:12
-
Journal article (peer-reviewed)abstract
- Neuroendocrine neoplasms (NENs) causing ectopic Cushing's syndrome (ECS) are rare and challenging to treat. In this retrospective cohort study, we aimed to evaluate different approaches for bilateral adrenalectomy (BA) as a treatment option in ECS. Fifty-three patients with ECS caused by a NEN (35 females/18 men; mean +/- SD age: 53 +/- 15 years) were identified from medical records. Epidemiological and clinical parameters, survival, indications for surgery and timing, as well as duration of surgery, complications and surgical techniques, were collected and further analysed. The primary tumour location was thorax (n = 30), pancreas (n = 14) or unknown (n = 9). BA was performed in 37 patients. Median time from diagnosis of ECS to BA was 2 months (range 1-10 months). Thirty-two patients received different steroidogenesis inhibitors before BA to control hypercortisolaemia. ECS resolved completely after surgery in 33 patients and severe peri- or postoperative complications were detected in 12 patients. There were fewer severe complications in the endoscopic group compared to open surgery (p = .030). Posterior retroperitoneoscopic BA performed simultaneously by a two surgeon approach had the shortest operating time (p = .001). Despite the frequent use of adrenolytic treatment, BA was necessary in a majority of patients to gain control over ECS. Complication rate was high, probably as a result of the combination of metastatic disease and metabolic disorders caused by high cortisol levels. The two surgeon approach BA may be considered as the method of choice in ECS compared to other BA approaches as a result of fewer complications and a shorter operating time.
|
|
| 17. |
- Santos, Licínia, et al.
(author)
-
Characterization of glycosphingolipids from gastrointestinal stromal tumours.
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually. In this study the acid and non-acid glycosphingolipids of three GISTs were characterized using a combination of thin-layer chromatography, chemical staining, binding of carbohydrate recognizing ligands, and mass spectrometry. In the non-acid glycosphingolipid fractions of the tumors globotetraosylceramide, neolactotetraosylceramide, and glycosphingolipids with terminal blood group A, B, H, Lex, Lea, Ley and Leb determinants were found. The relative amounts of these non-acid compounds were different in the three tumour samples. The acid glycosphingolipid fractions had sulfatide, and the gangliosides GM3, GD3, GM1, Neu5Acα3neolactotetraosylceramide, GD1a, GT1b and GQ1b. In summary, we have characterized the glycosphingolipids of GISTs and found that the pattern differs in tumours from different individuals. This detailed characterization of glycosphingolipid composition of GISTs could contribute to recognition of new molecular targets for GIST treatment and sub-classification.
|
|
| 18. |
- Säljö, Karin, 1981, et al.
(author)
-
Characterization of Glycosphingolipids in the Human Parathyroid and Thyroid Glands
- 2021
-
In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:13
-
Journal article (peer-reviewed)abstract
- As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x(2) glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Le(b) determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers.
|
|
| 19. |
- Säljö, Karin, 1981, et al.
(author)
-
Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers
- 2021
-
In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:19
-
Journal article (peer-reviewed)abstract
- Medullary thyroid carcinoma (MTC) accounts for only 1-2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Gal beta 4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Le(x), H type 2 and x(2) pentaosylceramides, the Le(y) and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (Gal alpha Gal beta 4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Le(y) in the MTC cells and also a variable intensity and prevalence of Globo H and Le(x). One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.
|
|
| 20. |
- Tegelberg, Alexander, 1974-
(author)
-
Managers and health professionals in the acute care chain : – A need for a shared understanding in the care of patients with acute abdominal pain
- 2021
-
Licentiate thesis (other academic/artistic)abstract
- Background: Managers and health professionals, so-called stakeholders, at the system and clinical level in the acute care chain, are responsible for providing safe and high-quality care encompassing both nursing and medical aspects. In patients with acute abdominal pain (AAP), high-quality nursing care has been described as not always being delivered across the entire acute care chain. This patient group frequently seeks care across the acute care chain and the care procedures and quality may differ widely. The quality of nursing care provided to patients can be understood through the framework Fundamentals of Care. The framework is divided into three dimensions: establishing a relationship with the patient, integration of the patient’s fundamental care needs, and context of care. Stakeholders are one important part of the context of care and a prerequisite for delivery of high-quality care. Aim: The overall aim was to explore managers’ and health professionals’ understanding of managing and conducting care of patients with AAP across the acute care chain. Method: Individual interviews with open-ended questions were used in two studies and data were analysed with a conventional qualitative content analysis method. Participants represented ambulance services, emergency departments, and surgical departments. Managers at head nurse level (n=11) and operational level (n=6) at four hospitals were included in Study I. Registered nurses (n=11) and physicians (n=8) at five hospitals were included in Study II.Results: In Study I, managers described the adult patient group as challenging and heterogenous. The managers reflected on themselves as role models. Guidelines were used to organise care, but they often had a medical focus and the managers referred to others as being responsible for the guidelines. Managers who were registered nurses focused on the medical care of patients with AAP, while managers who were physicians underlined the value of nursing care to improve patient outcome. In Study II, health professionals described dedication to applying evidence-based practices. However, they used personal experience over guidelines in care provision. They described organisational barriers to delivering high-quality care, such as varying competence among colleagues, lack of available patient beds, and lack of collaboration across the acute care chain. Conclusion: The stakeholders’ perspectives complemented each other, but their descriptions of managing and conducting care of patients with AAP did not always fit together, which revealed a gap in the everyday clinical practices as well as structural issues at the system level. These empirical descriptions of differing understanding may reveal some of the reasons why patients with AAP do not always experience high-quality care. To optimise patient care across the acute care chain, stakeholders need a shared understanding to meet patients’ fundamental care needs and enable provision of high-quality nursing and medical care.
|
|
