| 1. |
- Sorbye, H, et al.
(author)
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Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3) : the NORDIC NEC study
- 2013
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:1, s. 152-160
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Journal article (peer-reviewed)abstract
- As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67 < 55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67 < 55% had a lower response rate (15% versus 42%, P < 0.001), but better survival than patients with Ki-67 >= 55% (14 versus10 months, P < 0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67 < 55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.
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| 6. |
- Baudin, Eric, et al.
(author)
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Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms
- 2019
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 7-17
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Journal article (peer-reviewed)abstract
- Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.
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| 7. |
- Capdevila, Jaume, et al.
(author)
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Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms
- 2019
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 18-25
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Journal article (peer-reviewed)abstract
- Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.
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| 12. |
- Dumanski, Jan P., et al.
(author)
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Smoking is associated with mosaic loss of chromosome Y
- 2015
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6217, s. 81-83
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Journal article (peer-reviewed)abstract
- Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% CI = 2.8-6.7; ULSAM: OR = 2.4, 95% CI = 1.6-3.6; and PIVUS: OR = 3.5, 95% CI = 1.4-8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.
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| 14. |
- Fjallskog, Marie-Louise, et al.
(author)
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Expression of molecular targets for tyrosine kinase receptor antagonistsin malignant endocrine pancreatic tumors
- 2003
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 9:4, s. 1469-1473
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Journal article (peer-reviewed)abstract
- PURPOSE: Molecular targeting with monoclonal antibodies and tyrosine kinase inhibitors is a novel approach to cancer treatment. We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment. EXPERIMENTAL DESIGN: Thirty-eight tumor tissues from malignant endocrine pancreatic tumors were examined with immunohistochemistry using specific polyclonal antibodies with regard to the expression pattern of platelet-derived growth factor receptors (PDGFRs) alpha and beta, c-kit, and epidermal growth factor receptor (EGFR). RESULTS: All 38 tissue specimens expressed PDGFRalpha on tumor cells, and 21 of 37 specimens (57%) expressed PDGFRalpha in tumor stroma (1 specimen was nonevaluable). Twenty-eight samples (74%) stained positive for PDGFRbeta on tumor cells, and 36 of 37 samples (97%) stained positive for PDGFRbeta in the stroma (1 specimen was nonevaluable). Thirty-five tumor tissues (92%) stained positive for c-kit, and 21 (55%) stained positive for EGFR on tumor cells. No differences were seen between syndromes or between poorly differentiated or well-differentiated tumors. Previous treatment did not influence expression pattern. Receptor expression pattern varied considerably between individuals. CONCLUSIONS: We have found that tyrosine kinase receptors PDGFRs alpha and beta, EGFR, and c-kit are expressed in more than half of the patients with endocrine pancreatic tumors. Because these receptors represent molecular targets for STI571 and ZD1839 (tyrosine kinase inhibitors) and IMC-C225 (a monoclonal antibody), we propose that patients suffering from EPTs might benefit from this new treatment strategy. However, because of great variability in receptor expression pattern, all patients' individual receptor expression should be examined.
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| 15. |
- Fjällskog, Marie-Louise H., et al.
(author)
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Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors
- 2008
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 88:1, s. 53-8
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Journal article (peer-reviewed)abstract
- Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. BACKGROUND: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. METHODS: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m(2) of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. RESULTS: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. CONCLUSION: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination. 2008 S. Karger AG, Basel.
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| 27. |
- Saras, Jan, et al.
(author)
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Somatostatin induces rapid contraction of neuroendocrine cells
- 2007
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In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 581:10, s. 1957-1962
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Journal article (peer-reviewed)abstract
- The peptide hormone somatostatin, as well as the somatostatin analog octreotide, induces rapid morphological changes in neuroendocrine cells. The effect can be detected in less than 2min: retraction fibers are formed, cells round up and cell–cell contacts are broken. Somatostatin-dependent cell contraction is inhibited by Y-27632, indicating that this effect is dependent on Rho kinase. In BON1 cells, the somatostatin-induced inhibition of forskolin-induced secretion of chromogranin A is not blocked by Y-27632. It is therefore concluded that the inhibitory effect of somatostatin in forskolin-stimulated cells is not dependent on cell contraction.
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| 28. |
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| 29. |
- Tiensuu Janson, Eva, et al.
(author)
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[111In-DTPA-D-Phe1]octreotide scintigraphy in patients with carcinoid tumours : the predictive value for somatostatin analogue treatment
- 1994
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 131:6, s. 577-581
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Journal article (peer-reviewed)abstract
- This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy; of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication.
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| 30. |
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| 31. |
- Tiensuu Janson, Eva, et al.
(author)
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Carcinoid tumors : analysis of prognostic factors and survival in 301 patients from a referral center
- 1997
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In: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 8:7, s. 685-690
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Journal article (peer-reviewed)abstract
- BACKGROUND:Little is known about factors related to prognosis in patients with carcinoid disease. In this study we have tried to identify such factors.PATIENTS AND METHODS:We have evaluated 301 consecutive carcinoid patients (256 midgut, 39 foregut and six hindgut) referred during 15 years for medical treatment with respect to tumor distribution, hormone production, prognostic factors and survival.RESULTS:Survival was significantly shorter in midgut carcinoid patients with > or = 5 liver metastases or with high levels of urinary 5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. By univariate analysis, these variables together with the presence of carcinoid syndrome were related to a higher risk of dying. In multivariate analyses, performed in the 71 patients with full information on all variables, advanced age and plasma chromogranin A > 5000 micrograms/l were independent predictors of overall survival.CONCLUSIONS:Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.
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| 32. |
- Tiensuu Janson, E, et al.
(author)
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Carcinoid tumours
- 1996
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In: Clinical Gastroenterology.
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Book chapter (other academic/artistic)
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| 33. |
- Tiensuu Janson, E, et al.
(author)
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Malignant neuroendocrine tumors.
- 2002
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In: Cancer Chemother Biol Response Modif. ; , s. 463-
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Book chapter (other academic/artistic)
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| 38. |
- Tiensuu Janson, E, et al.
(author)
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The carcinoid syndrome
- 2005
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In: Gastroenterology and Hepatology: the Modern Clinician's Guide. - : Weinstein WM, Hawkey CJ and Bosch J. ; , s. 823-830
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Book chapter (other academic/artistic)
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| 39. |
- Tsolakis, Apostolos V., et al.
(author)
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Ghrelin Immunoreactive Cells in Gastric Endocrine Tumors and Their Relation to Plasma Ghrelin Concentration : Ghrelin in Gastric Endocrine Tumors
- 2008
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In: Journal of Clinical Gastroenterology. - 0192-0790 .- 1539-2031. ; 42:4, s. 381-388
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Journal article (peer-reviewed)abstract
- GOALS: Our aim was to elucidate the incidence and distribution pattern of ghrelin-immunoreactive (IR) cells in various types of human gastric endocrine tumors, and their surrounding mucosa, and relate the findings to total ghrelin concentrations in plasma. BACKGROUND: It has been demonstrated previously, that ghrelin-IR cells are present not only in normal human gastric oxyntic mucosa, but also in all types of enterochromaffinlike (ECL) cell carcinoids (ECL-CCs), and in mucosal regions affected by ECL cell hyperplasia. STUDY: Forty-eight gastric endocrine tumors were included in the study: 32 type I ECL-CCs, 3 type II, 9 type III, 1 non-ECL-CC, and 3 poorly differentiated endocrine carcinomas. The tumors were analyzed immunohistochemically with antibodies raised versus chromogranin A, synaptophysin, serotonin, somatostatin, vesicular monoamine transporter 2 and ghrelin. Total ghrelin in plasma was measured in 20 patients, using a commercial radioimmunoassay kit. RESULTS: Ghrelin-IR cells were found in all types I and II ECL-CCs but in only a few cases of the other tumors. Ghrelin-IR cells were also found among the hyperplastic endocrine cells in the mucosa surrounding types I and II, where they showed diffuse, linear, nodular and adenomatoid hyperplasia patterns. In type III ECL-CCs and poorly differentiated endocrine carcinomas, only diffuse and linear ghrelin-IR cell hyperplasia was present in the oxyntic mucosa in about half of the cases, whereas the mucosa of the non-ECL-CC did not show this feature. CONCLUSIONS: Despite the frequent occurrence of ghrelin-IR cells in both the neoplastic parenchyma and the oxyntic mucosa, plasma total ghrelin concentrations remained within the reference range and can therefore not be used as a clinical marker to identify ghrelin expressing ECL-CCs or ghrelin cell hyperplasia.
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| 40. |
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| 41. |
- Tsolakis, Apostolos V., et al.
(author)
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Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach
- 2009
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 160:6, s. 941-949
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Journal article (peer-reviewed)abstract
- Objective:Obestatin and ghrelin are derived from the same gene and co-expressed in the same endocrine cells. Vesicular monoamine transporter-2 (VMAT-2), a marker for enterochromaffin-like (ECL) cells, is considered to be expressed in ghrelin cells. The aim was to establish if the two peptides and the transporter are co-expressed, both in normal gastric mucosa and in gastric endocrine tumours.Design: An immunohistochemical study was performed on gastric biopsy material and on surgical specimens from 63 patients with gastric endocrine tumours and from individuals with normal gastric mucosa. Cells displaying obestatin immunoreactivity were examined regarding co-localization with ghrelin and VMAT-2. Both single- and double-immunostaining techniques were applied. Obestatin concentration in blood was measured in a subgroup of these patients. The results were correlated to various clinico-pathological parameters.Results:In the normal mucosa, obestatin/ghrelin-immunoreactive cells rarely co-expressed VMAT-2. In most tumour tissue specimens, only a fraction of neoplastic cells displayed immunoreactivity to obestatin, and these cells always co-expressed ghrelin. Neoplastic obestatin-/ ghrelin-IR cells invariably expressed VMAT-2, except for two ghrelinomas. The obestatin concentrations in blood were consistently low and did not correlate to clinico-pathological data.Conclusions:Obestatin and ghrelin immunoreactivity always occurred in the same endocrine cells in the gastric mucosa but these cells only occasionally co-expressed VMAT-2, opposite to the findings in tumours. These results indicate that endocrine cells expressing obestatin and ghrelin mainly differ from VMAT-2 expressing cells (ECL-cells) and can develop into pure ghrelinomas. Plasma concentrations of obestatin did not correlate to cellular expression.
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| 42. |
- Wedin, Maria, 1977-, et al.
(author)
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Rare metastases diagnosed on 68Ga-DOTATOC-PET/CT in small intestinal and pancreatic NETs
- 2023
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In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 35:Suppl. 1, s. 116-116
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Journal article (other academic/artistic)abstract
- Introduction: Neuroendocrine metastases to the orbita, heart, breast, bone, Virchow's lymph node, and pancreas are rarely encountered in small intestinal (SI-NETs) and pancreatic NETs (P-NETs).Aim(s): We aimed to assessthe prevalence of rare metastatic locations in patients with well-differentiated SI-NETs and P-NETs, who had undergone 68Ga-DOTATOC-PET/CT at diagnosis and/or follow-up.Materials and methods: In this retrospective analysis of 753 SI-NET patients and 418 P-NET patients treated at two tertiary referral centers, rare metastases were evident in 26.5% (310/1171) of the patient cohort.Results: Among patients with rare metastases (n=310), 45 % were women and median age at metastases diagnosis was 70 years (43-90). Median Ki-67 was 7% (1-70); 106 were G1 tumors, 142 G2, 11 G3 and 51 of unknown grade. Rare metastatic sites were present in bone 18 % (215/1171), Virchow's lymph node 6 % (75/1171) and 4 % (42/1171) in the lung/pleura. Metastases to the pancreas, breast, heart and orbita were only encountered in SI-NET primaries with a frequency of 5 % (41/753), 2 % (17/753), 2 % (14/753) and 2 % (12/753) respectively. Concomitant liver metastases were present in 86 %. Uncommon metastases were more frequent in SI-NET as compared with P-NET primaries, 255/753 [34%] vs. 55/418 [13%], p ˂0.00001. Bone metastases were present in 23 % (175/753) of SI-NET and 10 % (40/418) of p-NET primaries.Conclusion: In conclusion, rare metastases are more frequent in SI-NET than p-NETs. The variety and pattern of rare metastases seems different between SI-NETs and P-NET primaries, as orbita, heart, breast and Virchow's lymph node deposits were only encountered in SI-NETs patients; and bone metastases were approximately twice more often inthis group.
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