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- Galleberg, R. B., et al.
(author)
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Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas
- 2017
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:9, s. 1682-1689
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Journal article (peer-reviewed)abstract
- Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan Meier analyses for the entire cohort and for subgroups. Results: Median OS after resection/RFA of liver metastases was 35.9 months (95% -CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95% -CI: 3.9-13). Four patients (13%) were disease -free after 5 years. Two patients had well -differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 >= 55%. A Ki-67 < 55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA. Conclusion: This study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.
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- 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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- Dumanski, Jan P., et al.
(author)
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A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
- 2017
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In: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
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Journal article (peer-reviewed)abstract
- The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.
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- Elvebakken, Hege, et al.
(author)
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A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Its Clinical Correlations
- 2021
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In: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:9, s. 883-894
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Journal article (peer-reviewed)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are classified according to morphology as well-differentiated neuroendocrine tumours (NETs) G3 or poorly differentiated neuroendocrine carcinomas (NECs). Little data exist concerning which morphological criteria this subdivision should be based on. Uncertainty exists if the NEC group should be further subdivided according to proliferation rate. Clinical data on NET G3 and NEC with a lower Ki-67 range are limited. A total of 213 patients with high-grade GEP-NEN (Ki-67 >20%) were included from the Nordic NEC Registries. Four experienced NET pathologists re-evaluated the cases to develop the best morphological criteria to separate NET G3 from NEC, assuming longer survival in NET G3. Organoid growth pattern, capillary network in direct contact to tumour cells, and absence of desmoplastic stroma were found to best separate NET G3 from NEC. Of 196 patients with metastatic disease, NET G3 was found in 12.3%, NEC with a Ki-67 <55% (NEC < 55) in 29.6%, and NEC with a Ki-67 >= 55% (NEC >= 55) in 56.6%. Only in 1.5%, the morphology was ambiguous. Of 164 patients receiving first-line chemotherapy, 88% received platinum/etoposide treatment. Response rate was higher for NEC >= 55 (44%) than that of NEC < 55 (25%) and NET G3 (24%) (p = 0.025 and p = 0.026). Median progression-free survival was 5 months for all groups. Median overall survival was 33 months for NET G3 compared to 11 months for both NEC < 55 and NEC >= 55 (p = 0.004 and 0.003). Specific morphological criteria can separate NET G3 from NECs and show prognostic significance. High-grade GEP-NEN patients stratified by morphology and proliferation rate demonstrate significant differences in response to chemotherapy and survival.
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- Keskitalo, N., et al.
(author)
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Characterization of hydrophobic bonded silicon wafers
- 2002
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In: Nuclear Instruments and Methods in Physics Research Section B. - 0168-583X .- 1872-9584. ; 186, s. 66-70
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Journal article (peer-reviewed)abstract
- Direct bonding of silicon-to-silicon has been recognized as an interesting method for creating novel device geometries and structures and it has so far been used for the preparation of power devices and sensors. The influence of the bonded interface on electrical performance is then of great interest. In this contribution the interface region of hydrophobic bonded n-type silicon wafers have been studied and a comparison is made between samples before and after an exposure to low doses of 9.5 MeV protons to see the effect of the interface on point defect kinetics, The samples were studied using current-voltage (IV), capacitance-voltage (CV). deep level transient spectroscopy (DLTS). secondary ion mass spectrometry (SIMS) and scanning electron microscopy (SEM). During reverse bias there is a dramatic increase in leakage current when the depletion region reaches the bonded interface region. Due to the high leakage currents DLTS measurements could not be performed directly at the interface. However. in contrast to previous studies. no deep levels are discovered in the interface region of non-irradiated samples and, furthermore, no influence of the bonded interface on the concentration and depth distribution of irradiation induced defects could be detected. This suggests that the irradiation induced defects are unaffected by the bonded interlace, At the interface a boron peak is detected by SIMS.
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| 14. |
- Ljungberg, K., et al.
(author)
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Buried Cobalt Silicide Layers in Silicon Created by Wafer Bonding
- 1994
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In: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 141:10, s. 2829-2833
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Journal article (peer-reviewed)abstract
- A buried conductive layer in silicon has been created using wafer bonding technique, with a cobalt interfacial layer.Co-coated silicon wafers were brought into contact with either similar or uncoated wafers at room temperature. CoSi2 wasthen formed through a solid-phase reaction, during an anneal at 700 to 900°C. A 700 Å buried CoSi2-layer, with a resistivityof approximately 21 µ cm, was achieved. Good adhesion, as measured by tensile strength testing, between the wafers wasachieved. Transmission electron microscopic investigations (Co-coated wafer bonded to bare silicon) showed that thesilicide has not grown into the opposite wafer, and that an amorphous layer exists between the silicide and the siliconsurface. The presence of such a layer has been confirmed by electrical characterization.
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- Tiensuu Janson, Eva, et al.
(author)
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Treatment with alpha-interferon versus alpha-interferon in combinationwith streptozocin and doxorubicin in patients with malignant carcinoidtumors : a randomized trial
- 1992
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In: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 3:8, s. 635-638
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Journal article (peer-reviewed)abstract
- An open randomized trial was performed to compare the effect of recombinant interferon-alpha 2a (rIFN-alpha 2a) (group A, n = 12) versus rIFN-alpha 2a in combination with chemotherapy (group B, n = 11) in patients with malignant carcinoid tumors. Both groups received rIFN-alpha 2a at a dose of 3 MU/m2 s.c. three times weekly during the first 6 months. IFN was discontinued every third week in group B, followed by an i.v. injection of 2 g streptozocin and 40 mg/m2 doxorubicin. After 6 months group A showed one complete biochemical response (CR), 9 patients with stable disease (SD) and 2 who progressed (PD). Two patients had a partial reduction (PR) of tumor size, 9 showed SD and one PD. All patients in group B demonstrated SD. Chemotherapy was withdrawn after 6 months and all patients continued with rIFN-alpha 2a at an increased dose of 3 MU/m2 five days/week for a further 6 months. After 12 months 6 patients showed PR, 12 SD and one PD biochemically. Tumor size showed SD in 18 patients and PD in one. One patient died from cardiomyopathy, probably induced by doxorubicin. Antibodies against rIFN-alpha 2a developed in 41% of the patients. In conclusion, we detected no difference in response rates between the two treatment groups. Adverse reactions from the combination were considerable. The frequent development of IFN antibodies might have interfered with the therapeutic results.
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