| 1. |
- Falkmer, Ursula G., et al.
(författare)
-
Malignant presacral ghrelinoma with long-standing hyperghrelinaemia
- 2015
-
Ingår i: Uppsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:4, s. 299-304
-
Tidskriftsartikel (refereegranskat)abstract
- Background. A 57-year old man with low-back pain was found to have a 3 x 3 x 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist Lu-177-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination. Procedures. A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with Ga-68-labelled somatostatin analogues was used. Observations. The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and Ga-68-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).Conclusions. Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.
|
|
| 2. |
- Landerholm, Kalle, et al.
(författare)
-
Survival and prognostic factors in patients with small bowel carcinoid tumour
- 2011
-
Ingår i: British Journal of Surgery. - : Wiley-Blackwell. - 0007-1323 .- 1365-2168. ; 98:11, s. 1617-1624
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies of small bowel carcinoid tumours usually presented overall or relative survival. This study, in addition, evaluated disease-specific survival in a cohort of patients in a geographically defined population.METHODS: Patients diagnosed with carcinoid of the jejunum or ileum in Jönköping County between 1960 and 2005 were eligible for inclusion. Available tumour specimens were re-examined to confirm the diagnosis. Medical records and pathology reports were reviewed in detail.RESULTS: A total of 145 patients were included in the study. One hundred and thirty-five patients underwent surgery in connection with the diagnosis. Resection was considered complete (R0) in 74 patients (54·8 per cent). Only two localized tumours recurred, whereas no patient with distant metastases was cured. Patients with regional metastases who underwent R0 resection had a better survival than patients with incomplete resection (P = 0·005), and a majority of patients remained recurrence-free. Median overall survival was 7·2 years and median disease-specific survival 12·3 years. In multivariable analysis, age 61-74 years (hazard ratio (HR) 3·78, 95 per cent confidence interval 1·86 to 7·68), age 75 years or more (HR 3·96, 1·79 to 8·74), distant metastases (HR 14·44, 1·59 to 131·36) and incomplete tumour resection (HR 2·71, 1·11 to 6·61) were associated with worse disease-specific survival. Later time period of diagnosis (HR 0·45, 0·24 to 0·84) was associated with better disease-specific survival.CONCLUSION: Age, disease stage and complete resection were identified as independent prognostic factors for survival in patients with small bowel carcinoid tumours. The importance of achieving R0 resection is therefore emphasized.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Landerholm, Kalle, et al.
(författare)
-
Expression of Cocaine- and Amphetamine-Regulated Transcriptis Associated with Worse Survival in Small Bowel Carcinoid Tumors
- 2012
-
Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 18:13, s. 3668-3676
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cocaine- and amphetamine-regulated transcript (CART) peptide exerts several regulatory functions acting both as neurotransmitter and hormone. We recently showed that CART is expressed in various neuroendocrine tumors, including small bowel carcinoid. The main objective of the present study was to examine whether CART expression is associated with survival in small bowel carcinoid patients. Secondary aims were to assess if CART expression is associated with other tumor characteristics or clinical symptoms.Experimental Design: Specimens from 97 patients with small bowel carcinoids were examined for CART expression using immunohistochemistry and in situ hybridization. A CART score was introduced based on the proportion of CART immunoreactive cells. On inclusion, specimens were examined by routine histopathological methods and detailed clinical patient data were retrieved. The effect of CART on cell viability was assessed in vitro using an enteroendocrine cell line.Results: Expression of CART (P = 0.011), and increasing CART score (P = 0.033) were associated with worse disease-specific survival. Adjusting for age, disease stage and tumor grade in multivariable analysis, CART expression was still associated with worse survival (Low CART hazard ratio (HR) 5.47, 95% confidence interval (CI) 0.71 to 42.46; and High CART HR 9.44, 95% CI 1.14 to 78.14). Expression of CART correlated with higher tumor grade, but not with age or disease stage, neither with weight loss or any other symptom. Supporting our clinical data, we found that CART promoted tumor cell viability in vitro.Conclusion: Expression of CART in small bowel carcinoid tumors is associated with worse survival.
|
|
| 7. |
- Landerholm, Kalle, et al.
(författare)
-
Ki-67 Index and Solid Growth Pattern as Prognostic Markers in Small Intestinal Neuroendocrine Tumors
- 2015
-
Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 102:4, s. 327-334
-
Tidskriftsartikel (refereegranskat)abstract
- Background/aims: The prognostic value of histopathological grading and the growth pattern of small intestinal neuroendocrine tumors (SI-NET) is unclear. In particular, the cutoff level between grades G1 and G2 at Ki-67 index above 2% is an open issue, and both lower and higher cutoffs have been proposed. The morphological solid growth pattern (SGP) in SI-NET has been reported to be associated with worse survival. The present study investigates whether a Ki-67 index cutoff of 1% has a higher predictive power than one of 2% for disease-specific survival in SI-NET, and whether an SGP is associated with survival.Patients and methods: From a population-based cohort, 127 SI-NET patients with available tumor specimens were included. Medical records and pathology reports were reviewed. Tumor specimens were reexamined to confirm the diagnosis, recalculate the Ki-67 index, and assess the presence of an SGP, introducing an SGP score from 0 to 3+.Results: The current grading system with a G1/G2 cutoff of 2% was more discriminative (HR 2.30; 95% CI 1.20-4.38, p = 0.012) than one with a lower cutoff of 1% (HR 1.65; 95% CI 0.95-2.87, p = 0.078) after adjustment for patient age and clinical stage. SGP score was strongly associated with clinical stage (p = 0.004) and histopathological grade (p < 0.001) but was not an independent prognostic factor for disease-specific survival in SI-NET (p = 0.122) after adjusting for age, stage, and grade.Conclusions: The present grading system of SI-NET is supported by our results. The SGP is not an independent prognostic factor for disease-specific survival in SI-NET.
|
|
| 8. |
- Ma, Zuheng, et al.
(författare)
-
Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice
- 2011
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the beta-cell population and also to alpha-and delta-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse beta-cells. This duration effect on action potential in beta-cells from mceph/mceph mice was mimicked by dendrotoxin-K in beta-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. Conclusion/Significance: Kv1.1 channels are expressed in the beta-cells of several species, and these channels can influence glucose-stimulated insulin release.
|
|
| 9. |
|
|
| 10. |
|
|
