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  • 1. Ahlman, Håkan
    et al.
    Nilsson, Ola
    McNicol, Anne M.
    Ruszniewski, Philippe
    Niederle, Bruno
    Ricke, Jens
    Jensen, Robert
    Kos-Kudła, Beata
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    O'Connor, Juan M.
    Pavel, Marianne E.
    Vullierme, Marie-Pierre
    Poorly-differentiated endocrine carcinomas of midgut and hindgut origin2008Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 87, nr 1, s. 40-46Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Ali, Abir A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Grönberg, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Hjortland, G. O.
    Univ Oslo, Dept Oncol, Oslo, Norway.
    Grønbæk, H.
    Aarhus Univ Hosp, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Ladekarl, M.
    Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark.
    Langer, S. W.
    Rigshosp, Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Vestermark, L. W.
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Österlund, P.
    Tampere Helsinki Univ Hosp, Dept Oncol, Tampere, Finland.;Tampere Helsinki Univ, Tampere, Finland.
    Knigge, U.
    Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Surg C, Copenhagen, Denmark; Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Endocrinol PE, Copenhagen, Denmark.
    Sørbye, H.
    Univ Bergen, Haukeland Univ Hosp, Dept Oncol, Bergen, Norway; Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Intravenous versus Oral Etoposide: Efficacy and Correlation to Clinical Outcome in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 184-184Artikkel i tidsskrift (Annet vitenskapelig)
  • 3.
    Alit, Abir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Grönberg, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Federspiel, B.
    Dept Pathol, Copenhagen, Denmark..
    Hjortland, G. O.
    Dept Oncol, Oslo, Norway..
    Ladekarl, M.
    Dept Oncol, Aarhus, Denmark..
    Langer, S. W.
    Dept Oncol, Copenhagen, Denmark..
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Knigge, U.
    Dept Surg C, Copenhagen, Denmark.;Dept Endocrinol PE, Copenhagen, Denmark..
    Sorbye, H.
    Dept Oncol, Bergen, Norway..
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Expression of Mutated p53 Protein in Gastroenteropancreatic Neuroendocrine Carcinoma (WHO G3)2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 43-43Artikkel i tidsskrift (Fagfellevurdert)
  • 4.
    Almquist, M.
    et al.
    Skane Univ Hosp, Dept Surg, Lund, Sweden..
    Myrenfors, P.
    IPSEN, Stockholm, Sweden..
    Strom, T.
    IPSEN, Stockholm, Sweden..
    Kozlovacki, Gordana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    STREET - Somatostatin Treatment Experience Trial2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 191-191Artikkel i tidsskrift (Annet vitenskapelig)
  • 5.
    Anthony, L.
    et al.
    Univ Kentucky, Lexington, KY USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Hoersch, D.
    Zent Klin Bad Berka, Bad Berka, Germany..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Lombard-Bohas, C.
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Kunz, P.
    Stanford Univ, Palo Alto, CA 94304 USA..
    Valle, J. W.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England..
    Kassler-Taub, K.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Fleming, R.
    Charite, Berlin, Germany..
    Pavel, M.
    Charite, Berlin, Germany..
    Impact of Concomitant Medication on Efficacy of Telotristat Ethyl - A Post Hoc Subgroup Analysis of the Phase 3 TELESTAR Study in Carcinoid Syndrome2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 212-212Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Anthony, Lowell B.
    et al.
    Univ Kentucky, Markey Canc Ctr, Div Med Oncol, Lexington, KY 40536 USA..
    Pavel, Marianne E.
    Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany..
    Hainsworth, John D.
    Sarah Cannon Res Inst, Nashville, TN USA..
    Kvols, Larry K.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Segal, Scott
    Novartis Pharmaceut, E Hanover, NJ USA..
    Hoersch, Dieter
    Zentralklin Bad Berka GmbH, Klin Innere Med Gastroenterol & Endokrinol, Zentrum Neuroendokrine Tumore, Bad Berka, Germany..
    Van Cutsem, Eric
    Univ Hosp Gasthuisberg, Leuven, Belgium..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Yao, James C.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Impact of Previous Somatostatin Analogue Use on the Activity of Everolimus in Patients with Advanced Neuroendocrine Tumors: Analysis from the Phase III RADIANT-2 Trial2015Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, nr 1-2, s. 18-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: The phase III placebo-controlled RADI-ANT-2 trial investigated the efficacy of everolimus plus octreotide long-acting repeatable (LAR) in patients with advanced neuroendocrine tumors (NET) associated with carcinoid syndrome. Here we report a secondary analysis based on the previous somatostatin analogue (SSA) exposure status of patients enrolled in RADIANT-2. Methods: Patients were randomly assigned to receive oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscularly (i.m.) or to receive matching placebo plus octreotide LAR 30 mg i.m. every 28 days. SSA treatment before study enrollment was permitted. Patient characteristics and progression-free survival (PFS) were analyzed by treatment arm and previous SSA exposure status. Results: Of the 429 patients enrolled in RADI-ANT-2, 339 were previously exposed to SSA (95% received octreotide); 173 of 339 patients were in the everolimus plus octreotide LAR arm. All patients had a protocol-specified history of secretory symptoms, but analysis by type showed that more patients who previously received SSA therapy had a history of flushing symptoms (77%), diarrhea (86%), or both (63%) compared with SSA-naive patients (62, 62, and 24%, respectively). Patients who received everolimus plus octreotide LAR had longer median PFS regardless of previous SSA exposure (with: PFS 14.3 months, 95% confidence interval, CI, 12.0-20.1; without: 25.2 months, 95% CI, 12.0-not reached) compared with patients who received placebo plus octreotide LAR (with: 11.1 months, 95% CI, 8.4-14.6; without: 13.6 months, 95% CI, 8.2-22.7). Conclusion: Everolimus in combination with octreotide improves PFS in patients with advanced NET associated with carcinoid syndrome, regardless of previous SSA exposure.

  • 7.
    Antonodimitrakis, Pantelis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, nr 3-4, s. 345-353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In our center, the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU.

    PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated.

    RESULTS: Median survival from start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100) progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from start of treatment, respectively. Having either a G3 tumor or stage IV tumor were significant prognostic factors for shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side-effects, of which kidney toxicity (mainly grade 1-2) was the most frequent.

    CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response, and has an acceptable toxicity profile.

  • 8. Arnold, Rudolf
    et al.
    Chen, Yuan-Jia
    Costa, Frederico
    Falconi, Massimo
    Gross, David
    Grossman, Ashley B
    Hyrdel, Rudolf
    Kos-Kudła, Beata
    Salazar, Ramon
    Plöckinger, Ursula
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation2009Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 90, nr 2, s. 227-233Artikkel i tidsskrift (Fagfellevurdert)
  • 9.
    Barazeghi, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Prabhawa, Surendra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Uppsala Univ, Uppsala Univ Hosp, Rudbeck Lab, Uppsala, Sweden..
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    A Role of TETs and 5-Hydroxymethylcytosine in SI-NETs2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 18-18Artikkel i tidsskrift (Annet vitenskapelig)
  • 10.
    Baudin, Eric
    et al.
    Inst Gustave Roussy, Oncol Endocrinienne & Med Nucl, Villejuif, France.
    Hayes, Aimee R.
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Scoazec, Jean-Yves
    Univ Lyon, Dept Pathol, Lyon, France.
    Filosso, Pier Luigi
    Univ Torino, Dept Thorac Surg, Turin, Italy.
    Lim, Eric
    Royal Brompton Hosp, Dept Thorac Surg, London, England.
    Kaltsas, Gregory
    Natl Univ Athens, Div Endocrinol, Dept Pathophysiol, Athens, Greece.
    Frilling, Andrea
    Imperial Coll London, Dept Surg & Canc, London, England.
    Chen, Jie
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China.
    Kos-Kudła, Beata
    Slaska Akad Med, Klin Endokrynol, Zabrze, Poland.
    Gorbunova, Vera
    Russian Acad Med Sci, FSBI NN Blokhin Russian Canc Res Ctr, Moscow, Russia.
    Wiedenmann, Bertram
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Gastroenterol & Hepatol, Berlin, Germany; Charite Univ Med Berlin, Campus Virchow Klinikum, Berlin, Germany.
    Nieveen van Dijkum, Els
    Acad Med Ctr, Dept Surg, Amsterdam, Netherlands.
    Ćwikła, Jaroslaw B
    Univ Warmia & Mazury, Fac Med Sci, Dept Radiol, Olsztyn, Poland.
    Falkerby, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Valle, Juan W.
    Univ Manchester, Inst Canc Sci, Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England.
    Kulke, Matthew H
    Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
    Caplin, Martyn E
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Sundin, Anders ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tiensuu Janson, Eva ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Welin, Staffan ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, nr 1, s. 7-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 11. Bodei, Lisa
    et al.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kidd, Mark
    Prasad, Vikas
    Modlin, Irvin M
    The Status of Neuroendocrine Tumor Imaging: From Darkness to Light?2015Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 101, nr 1, s. 1-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diagnostic imaging plays a pivotal role in the diagnosis, staging, treatment selection and follow-up for neuroendocrine tumors. The available diagnostic strategies are morphologic imaging, including computed tomography, magnetic resonance imaging (MRI) and ultrasound techniques, and molecular imaging, including scintigraphy with 111In-pentetreotide and positron emission tomography with 68Ga-DOTA-peptides, 18F-DOPA and 11C-5-HTP. A combination of anatomic and functional techniques is routinely performed to optimize sensitivity and specificity. The introduction of diffusion-weighted MRI and dynamic contrast-enhanced techniques represents a promising advance in radiologic imaging, whereas new receptor-binding peptides, including somatostatin agonists and antagonists, represent the recent most favorable innovation in molecular imaging. Future development includes the short-term validation of these techniques, but in extension also a more comprehensive multilevel integration of biologic information pertaining to a specific tumor and patient, possibly encompassing genomic considerations, currently evolving as a new entity denoted ‘precision medicine'. The ideal is a diagnostic sequence that captures the global status of an individual's tumor and encompasses a multidimensional characterization of tumor location, metabolic performance and target identification. To date, advances in imagery have focused on increasing resolution, discrimination and functional characterization. In the future, the fusion of imagery with the parallel analysis of biological and genomic information has the potential to considerably amplify diagnosis.

  • 12.
    Botling, Johan
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Lamarca, Angela
    Bajic, Dragan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lönngren, Vincent
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Kjaer, Josefin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Rindi, Guido
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    High-grade progression confers poor survival in pancreatic neuroendocrine tumors.2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 13.
    Capdevila, Jaume
    et al.
    Vall Hebron Univ Hosp, VHIO, Barcelona, Spain.
    Bodei, Lisa
    Mem Sloan Kettering Canc Ctr, New York, NY USA.
    Davies, Philippa
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Gorbounova, Vera
    Inst Russian Acad Med Sci, Dept Oncol, Moscow, Russia.
    Jensen, Robert T.
    NIH, Bethesda, MD USA.
    Knigge, Ulrich P.
    Univ Copenhagen, Dept Surg, Copenhagen, Denmark.
    Krejs, Guenter J.
    Med Univ Graz, Graz, Austria.
    Krenning, Eric
    Erasmus MC, Cyclotron Rotterdam BV, Rotterdam, Netherlands.
    O'Connor, Juan Manuel
    Alexander Fleming Inst, Caba, Argentina.
    Peeters, Marc
    Antwerp Univ Hosp, Dept Oncol, Antwerp, Belgium.
    Rindi, Guido
    Univ Cattolica Sacro Cuore, Fdn Policlin Univ A Gemelli IRCCS Roma, Rome, Italy.
    Salazar, Ramon
    Catalan Inst Oncol, Oncobell Program, IDIBELL, Cerca,Ciberonc, Barcelona, Spain.
    Vullierme, Marie-Pierre
    Beaujon Hop Assistance Publ, Radiol Dept, Paris, France.
    Pavel, Marianne E.
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Erlangen, Germany.
    Sundin, Anders ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tiensuu Janson, Eva ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Welin, Staffan ()
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, nr 1, s. 18-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 14. Caplin, Martyn
    et al.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Nillson, Ola
    Baum, Richard P
    Klose, Klaus J
    Kelestimur, Fahrettin
    Plöckinger, Ursula
    Papotti, Mauro
    Salazar, Ramon
    Pascher, Andreas
    ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms2012Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 95, nr 2, s. 88-97Artikkel i tidsskrift (Fagfellevurdert)
  • 15.
    Chatzellis, Eleftherios
    et al.
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece;251 HAF & VA Hosp, Athens, Greece.
    Angelousi, Anna
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Daskalakis, Kosmas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Tsoli, Marina
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Alexandraki, Krystallenia I.
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Wachula, Ewa
    Med Univ Silesia, Dept Clin Oncol & Radiotherapy, Katowice, Poland.
    Meirovitz, Amichay
    Hadassah Hebrew Univ Med Ctr, Dept Oncol, Jerusalem, Israel;Hadassah Hebrew Univ Med Ctr, Radiat Therapy Unit, Jerusalem, Israel.
    Maimon, Ofra
    Hadassah Hebrew Univ Med Ctr, Dept Oncol, Jerusalem, Israel;Hadassah Hebrew Univ Med Ctr, Radiat Therapy Unit, Jerusalem, Israel.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ Med Ctr, Dept Endocrinol & Metab, Neuroendocrine Tumour Unit, Jerusalem, Israel.
    Gross, David
    Hadassah Hebrew Univ Med Ctr, Dept Endocrinol & Metab, Neuroendocrine Tumour Unit, Jerusalem, Israel.
    Kos-Kudla, Beata
    Med Univ Silesia, Dept Endocrinol & Neuroendocrine Neoplasms, Dept Endocrinol & Pathophysiol, Katowice, Poland.
    Koumarianou, Anna
    Univ Athens, Attikon Univ Gen Hosp, Hematol Oncol Unit, Dept Internal Med 4, Athens, Greece.
    Kaltsas, Gregory
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 109, nr 4, s. 333-345Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. Methods: Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. -Results: Seventy-nine patients with gastroenteropancreatic (grades 1-2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6-55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6-14.2) and 102.9 months (43.3-162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1-0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11-4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3-4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). Conclusions: CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.

  • 16.
    Chatzellis, Eleftherios
    et al.
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece;251 HAF & VA Hosp, 3 Kanelopoulou Ave, GR-11525 Athens, Greece.
    Daskalakis, Kosmas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Angelousi, Anna
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Tsoli, Marina
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Alexandraki, Krystallenia I.
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Wachula, Ewa
    Med Univ Silesia, Dept Clin Oncol & Radiotherapy, Katowice, Poland.
    Meirovitz, Amichay
    Hadassah Hebrew Univ, Oncol Dept, Med Ctr, Jerusalem, Israel;Hadassah Hebrew Univ, Radiat Therapy Unit, Med Ctr, Jerusalem, Israel.
    Maimon, Ofra
    Hadassah Hebrew Univ, Oncol Dept, Med Ctr, Jerusalem, Israel;Hadassah Hebrew Univ, Radiat Therapy Unit, Med Ctr, Jerusalem, Israel.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Dept Endocrinol & Metab, Med Ctr, Neuroendocrine Tumor Unit, Jerusalem, Israel.
    Gross, David
    Hadassah Hebrew Univ, Dept Endocrinol & Metab, Med Ctr, Neuroendocrine Tumor Unit, Jerusalem, Israel.
    Kos-Kudla, Beata
    Med Univ Silesia, Dept Endocrinol & Neuroendocrine Neoplasms, Katowice, Poland;Med Univ Silesia, Dept Pathophysiol & Endocrinol, Katowice, Poland.
    Koumarianou, Anna
    Univ Athens, Attikon Univ Gen Hosp, Dept Internal Med 4, Hematol Oncol Unit, Athens, Greece.
    Kaltsas, Gregory
    Univ Athens, Dept Propaedeut Internal Med 1, Athens, Greece.
    Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms: The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms"2020Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, nr 1-2, s. 158-160Artikkel i tidsskrift (Annet vitenskapelig)
  • 17. Costa, F.
    et al.
    Domenichini, E.
    Garavito, G.
    Medrano, R.
    Mendez, G.
    O'Connor, J.
    Rojas, W.
    Torres, S.
    Younes, R. N.
    Delle Fave, G.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Management of neuroendocrine tumors: a meeting of experts from Latin America2008Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 88, nr 3, s. 235-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

  • 18.
    Crona, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Secondary Hormonal Syndromes in Patients with Sporadic Neuroendocrine Tumors2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, nr 3-4, s. 240-240Artikkel i tidsskrift (Annet vitenskapelig)
  • 19.
    Crona, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Fanola, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lindholm, Daniel P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Antonodimitrakis, Pantelis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Effect of Temozolomide in Patients with Metastatic Bronchial Carcinoids2013Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 98, nr 2, s. 151-155Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Metastatic bronchial carcinoids are rare neoplasms, where efforts of medical treatment so far have been disappointing. A previous study from our center indicated that temozolomide might be of value. Materials and Methods: All patients with progressive metastatic bronchial carcinoid treated with tennozolomide as monotherapy at our center between 2004 and 2010 (n = 31) were included in this retrospective study. 14 tumors were classified as typical and 15 as atypical carcinoids, whereas 2 tumors could not be classified. Temozolomide was given on 5 consecutive days every 4 weeks. Toxicity was evaluable in 28 of 31 patients, and 22 patients were evaluable by RECIST 1.1. Results: There were no complete responses. A partial response was seen in 3 patients (14%), stable disease in 11(52%) and progressive disease in 7 patients (33%). Median progression-free survival was 5.3 months and median overall survival was 23.2 months from the start of temozolomide. Toxcities grade 3-4 were noted in 4 patients, thrombocytopenia (n =3) and leukopenia (n = 1). Conclusion: Temozolomide as monotherapy shows activity in metastatic bronchial carcinoids. Regimens combining tennozolomide with other agents (e.g. capecitabine and/or bevacizumab, everolimus, radiolabeled somatostatin analogues) should be further studied in these patients. Copyright (C) 2013 S. Karger AG, Basel

  • 20.
    Crona, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lamarca, A.
    Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England.
    Ronot, M.
    Beujon Univ Hosp, Dept Radiol, Clichy, France.
    Opalinska, M.
    Univ Hosp, Dept Endocrinol, Nucl Med Unit, Krakow, Poland.
    Lopez Lopez, C.
    Hosp Univ Marques de Valdecilla, Dept Med Oncol, Santander, Spain.
    Pezzutti, D.
    Israelita Albert Einstein Hosp, Dept Radiol, Sao Paulo, Brazil.
    Vidal Trueba, H.
    Hosp Univ Marques de Valdecilla, Dept Radiol, Santander, Spain.
    Carvhalo, L.
    Sirio Libanes Hosp, Dept Med Oncol, Sao Paulo, Brazil.
    de Mestier, L.
    Beujon Univ Hosp, Dept Gastroenterol, Clichy, France.
    Najran, P.
    Christie NHS Fdn Trust, Dept Radiol, Manchester, Lancs, England.
    Pavel, M.
    Univ Klinikum Erlangen, Dept Endocrinol, Erlangen, Germany.
    Dromain, C.
    CHUV Univ Hosp, Dept Radiol, Lausanne, Switzerland.
    Pre-Treatment Tumor Growth Rate (TGR0) in Patients Diagnosed with Well-Differentiated Neuroendocrine Tumors (NETs) Treated with Systemic Therapies: Subgroup Analysis of the GREPONET Study2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 171-171Artikkel i tidsskrift (Annet vitenskapelig)
  • 21.
    Crona, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Targeted Next Generation Sequencing in the Screening for Familial Neuroendocrine Tumor Syndromes: A Tool for Personalized Medicine2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, nr 3-4, s. 253-253Artikkel i tidsskrift (Annet vitenskapelig)
  • 22.
    Dam, G.
    et al.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Grønbæk, H.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Sørbye, H.
    Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Thiis-Evensen, E.
    Natl Hosp Norway, Oslo Univ Hosp, Dept Transplantat Med, Neuroendocrine Tumor Ctr Excellence, Oslo, Norway.
    Paulsson, B.
    Novartis Sverige AB, Täby, Sweden.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jensen, C.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Copenhagen, Denmark.
    Ebbesen, D.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Aarhus, Denmark.
    Knigge, U.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Endocrinol, Copenhagen, Denmark.;Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Surg Gastroenterol, Copenhagen, Denmark.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    A Prospective Nordic Study on the Use of Chromogranin A for the Prediction of Progression in Patients with Pancreatic and Small Intestinal Neuroendocrine Tumors2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 152-152Artikkel i tidsskrift (Annet vitenskapelig)
  • 23. Dam, Gitte
    et al.
    Grønbæk, Henning
    Sorbye, Halfdan
    Thiis Evensen, Espen
    Paulsson, Björn
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jensen, Claus
    Ebbesen, Dyveke
    Knigge, Ulrich
    Tiensuu Janson, Eva
    Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors.2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Retrospective studies are conflicting but most report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively we investigated if changes in plasma CgA was associated with tumor burden changes in NET patients with disseminated disease. Methods We included 239 patients from five NET centers between 2010-2013. CgA was measured within six weeks of a CT or an MRI in a patient undergoing at least two scan examinations performed with 1-24 months interval. In a post-hoc analysis, CgA measured 3-6 month prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased or unchanged levels. Results In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements) we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p<0.05). Of 304 events in the post-hoc analysis, 58 showed progression, 228 stable disease, and 18 regression with a median change in CgA +19%(IQR:57-(-20)), -12%(+23-(-38)) and -73%(-55-(-83)), respectively. The correlation coefficients for all sites were 0.17(p=0.003); and 0.16(p=0.07), 0.18(p=0.04); and 0.20(p=0.21) for small intestinal (n=137), pancreatic (n=123) and unknown primary NET (n=40), respectively. In the 58 events showing tumor progression, sensitivity and specificity of an increased CgA concentration were 36% and 82% with positive and negative predictive values of 32% and 85%. Conclusions In this prospective study of GEP-NET patients we observed only a weak association between change in plasma CgA and change in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.

  • 24.
    Daskalakis, Kosmas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Edfeldt, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Karakatsanis, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Midkine Is a New Novel Serum Biomarker in Small Intestinal Neuroendocrine Tumors (SI-NETs)2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 45-45Artikkel i tidsskrift (Fagfellevurdert)
  • 25.
    Daskalakis, Kosmas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Kaltsas, Gregory
    Univ Athens, Laiko Hosp, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Athens, Greece.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Tsolakis, Apostolos V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden; Karolinska Univ Hosp, Canc Ctr Karolinska, CCK, Stockholm, Sweden.
    Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 107, nr 4, s. 355-365Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Lung carcinoids (LCs) are often diagnosed at an early stage and surgical intervention becomes the next phase of treatment. To date, there is lack of long-term follow-up data after surgery and prognostication based on WHO classification criteria and evolving prognostic markers, particularly the expression of somatostatin receptors (SSR).

    Methods: We included 102 consecutive patients (72 women; age at baseline 51 ± 16 years [mean ± SD]) with LCs, who underwent thoracic surgery (n = 99) and/or laser treatment (n = 8). Hospital charts were reviewed for clinico-pathological parameters. Immunohistochemical (IHC) expression of SSR1–5 and other novel markers were studied with regard to their prognostic value.

    Results: Five- and 10-year overall survival (OS) was 96 and 83% respectively; relative survival (RS) was 101 and 93% respectively; and event-free survival (EFS) was 80 and 67% respectively. Independent prognostic factors for OS, RS and/or EFS were age at diagnosis, histopathological type and the presence of ipsilateral mediastinal subcarinal lymph node metastases. Macro-radicality of resective surgery and its extent were associated with increased OS and EFS. The IHC expression of SSR1–5 and other novel markers was not associated with OS or EFS.

    Conclusion: The long-term outcome of surgically treated patients with LCs is favourable. Age, histopathological type and ipsilateral mediastinal subcarinal lymph node status at baseline were independent prognostic factors for survival and disease recurrence or progression. The extent of surgery and operative macro-radicality also had an impact on prognosis. None of the IHC markers tested appeared to be associated with disease prognosis.

  • 26.
    Daskalakis, Kosmas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Karakatsanis, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ex Vivo Activity of Cytotoxic Drugs and Targeted Agents in Small Intestinal Neuroendocrine Tumors2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 189-189Artikkel i tidsskrift (Annet vitenskapelig)
  • 27.
    Daskalakis, Kosmas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece.
    Tsoli, Marina
    Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece.
    Srirajaskanthan, Raj
    Kings Coll Hosp London, Neuroendocrine Tumour Unit, Kings Coll Hosp, KHP ENETS Ctr Excellence,Dept Gastroenterol, London SE5 9RS, England.
    Chatzellis, Eleftherios
    Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece.
    Alexandraki, Krystallenia
    Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece.
    Angelousi, Anna
    Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece.
    Pizanias, Michail
    Kings Coll Hosp London, Dept Liver Transplantat, Inst Liver Studies,Hepatobiliary Pancreat Surg, Kings Healthcare Partners,NHS FT, Denmark Hill, London, England.
    Randeva, Harpal
    Univ Warwick, Warwick Med Sch, Clin Sci Res Labs, Univ Hosp, Coventry, W Midlands, England;Coventry Univ, Ctr Appl Biol & Exercise Sci, Fac Hlth & Life Sci, Coventry, W Midlands, England.
    Kaltsas, Gregory
    Univ Athens, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Laiko Hosp, Athens, Greece;Univ Warwick, Warwick Med Sch, Clin Sci Res Labs, Univ Hosp, Coventry, W Midlands, England;Coventry Univ, Ctr Appl Biol & Exercise Sci, Fac Hlth & Life Sci, Coventry, W Midlands, England.
    Weickert, Martin O.
    Univ Hosp Coventry & Warwickshire NHS Trust, ARDEN NET Ctr, European Neuroendocrine Tumour Soc ENETS, Ctr Excellence CoE, Coventry, W Midlands, England;Univ Warwick, Warwick Med Sch, Clin Sci Res Labs, Univ Hosp, Coventry, W Midlands, England;Coventry Univ, Ctr Appl Biol & Exercise Sci, Fac Hlth & Life Sci, Coventry, W Midlands, England.
    Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, nr 4, s. 308-316Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: To evaluate the impact of lung metastases (LM) on overall survival (OS) in well-differentiated (WD) stage IV gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) patients along with developing surveillance strategies for thoracic imaging. Methods: Thirty-four patients with LM, from 3 centres, were identified (22 small intestine/12 pancreatic; 17 grade 1/15 grade 2/2 of unknown grade). For comparison, we used 106 stage IV WD, grade 1 and 2 GEP-NEN patients with metastatic disease confined in the abdomen. Results: LM prevalence was 4.9% (34/692). Eleven patients (32%) presented with synchronous LM whereas 23 (68%) developed metachronous LM at a median of 25 months (range 1-150 months). Patients with metachronous LM had already established liver and/or para-aortic lymph node metastases. Eighteen of 23 patients (78%) with metachronous LM exhibited concomitant progression in the abdomen. Median OS of WD GEP-NEN patients with LM was shorter than for those with stage IV disease without extra-abdominal metastases (56 [95% CI 40.6-71.6] vs. 122.7 [95% CI 70.7-174.8] months; log-rank p = 0.001). Among patients with progressive stage IV disease, the subset of patients with LM exhibited shorter OS (log-rank p = 0.005). LM were also confirmed as an independent prognostic factor for survival in multivariable analysis (HR 0.18; 95% CI 0.07-0.45; p< 0.0001). Conclusion: LM, although relatively rare in patients with WD stage IV GEP-NENs, may impact patients' outcome. The development of metachronous LM is associated with concomitant disease progression in established abdominal metastases in most patients. These patient-related parameters could be utilized for a stratified surveillance approach, mainly reserving thoracic imaging for GEP-NEN patients with progressive disease in the abdomen.

  • 28. de Herder, Wouter W
    et al.
    Capdevila, Jaume
    Unmet Needs in the Field of Neuroendocrine Neoplasms of the Gastrointestinal Tract, Pancreas, and Respiratory System: Reports by the ENETS Group.2019Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, nr 1, s. 5-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    On the 10th and 11th of November 2016, 54 international experts in the field of neuroendocrine neoplasms (NEN) of the gastrointestinal tract, pancreas, and respiratory system met in Munich, Germany, to discuss and determine unmet needs in this field. The participating experts were Advisory Board members and invited guests of the European Neuroendocrine Tumor Society (ENETS). The Board members were medical specialists with different clinical or preclinical backgrounds, basic scientists, specialized nurses, and patient representatives.

    According to the Oxford dictionary, “unmet” refers to something (here, a need) which has not been achieved or fulfilled. The NEN expert subgroups succeeded in producing 6 reports on what they identified as the most relevant unmet needs in NEN. They identified several limitations of the current tumor classification, grading, and staging systems for almost all NEN subtypes.

    Apart from the historical separation regarding origin into foregut, midgut, and hindgut, other subentities have now been recognized, each requiring a more tailored approach. There is still a general lack of predictive and prognostic markers, in samples of both tumor tissue and surrogate tissues such as the blood. Tumor visualization making use of radiology and nuclear medicine has seen impressive advances in recent years. However, with regard to determining tumor (metastases) responses, there is still debate as to how best to achieve this with different imaging modalities.

    In spite of more treatment options (locoregional and systemic) being available for metastatic NENs, help is needed to select appropriate treatment strategies (sequencing) and there is also a need for more effective treatments. For some tumor entities, watchful waiting might be considered (e.g., in the case of small pancreatic NENs) but, again, the lack of reliable markers makes it difficult to decide which tumors should undergo resection and which should be monitored only. There are currently no registered or approved adjuvant treatment options for the period after curative resection of some of the isolated or locally advanced NENs (e.g., of the pancreas, appendix, and rectum). It is also unclear which patients might benefit from adjuvant treatment. The follow-up of patients with NENs remains a poorly studied area and is based on loose empirical international guidelines or institutional opinion.

    All of these unmet needs in the field of NENs exponentially increase the complexity of conducting well-designed clinical and translational studies to resolve these issues, with multidisciplinary and international efforts such as the current one led by ENETS being the only way to move forward. We invite all Readers of Neuroendocrinology interested in the field of NENs to study the series of 6 articles reporting on unmet needs in the field of NENs

    Fulltekst (pdf)
    fulltext
  • 29. de Herder, Wouter W.
    et al.
    Niederle, Bruno
    Scoazec, Jean-Yves
    Pauwels, Stanislas
    Kloppel, Gunter
    Falconi, Massimo
    Kwekkeboom, Dik J.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wiedenmann, Bertram
    Rindi, Guido
    O'Toole, Dermot
    Ferone, Diego
    Well-differentiated pancreatic tumor/carcinoma: insulinoma2006Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 84, nr 3, s. 183-188Artikkel i tidsskrift (Fagfellevurdert)
  • 30.
    Delle Fave, G.
    et al.
    Osped St Andrea, Dept Digest & Liver Dis, Rome, Italy.;Univ Roma La Sapienza, Dept Digest & Liver Dis, Via Grottarossa 1035, IT-00189 Rome, Italy..
    O'Toole, D.
    St Vincents Univ, NET Ctr, Dublin, Ireland.;St James Hosp, Dept Clin Med, Dublin 8, Ireland.;Univ Dublin Trinity Coll, Dublin 2, Ireland..
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Taal, B.
    Netherlands Canc Ctr, Lijnden, Netherlands..
    Ferolla, P.
    Univ Perugia, Umbria Reg Canc Network, NET Ctr, I-06100 Perugia, Italy..
    Ramage, J. K.
    Hampshire Hosp NHS Trust, Dept Gastroenterol, Winchester, Hants, England..
    Ferone, D.
    Univ Genoa, Dept Endocrine & Metab Sci, Genoa, Italy..
    Ito, T.
    Kyushu Univ Hosp, Pancreat Dis Branch, Fukuoka 812, Japan..
    Weber, W.
    Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA..
    Zheng-Pei, Z.
    Beijing Union Med Coll Hosp, Dept Endocrinol, Beijing, Peoples R China..
    De Herder, W. W.
    Erasmus MC, Div Endocrinol, Dept Internal Med, Rotterdam, Netherlands..
    Pascher, A.
    Charite, Dept Visceral & Transplant Surg, Campus Virchow Klinikum, D-13353 Berlin, Germany..
    Ruszniewski, P.
    Beaujon Hosp, Dept Gastroenterol, Clichy, France..
    ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, nr 2, s. 119-124Artikkel i tidsskrift (Fagfellevurdert)
  • 31.
    Dillon, J.
    et al.
    Univ Iowa, Iowa City, IA USA.
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA USA.
    Warner, R.
    Icahn Sch Med Mt Sinai, New York, NY USA.
    Bergsland, E.
    Univ Calif San Francisco, San Francisco, CA USA.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    O'Dorisio, T.
    Univ Iowa, Iowa City, IA USA.
    Mckee, C.
    Lexicon Pharmaceut, The Woodlands, TX USA.
    Lapuerta, P.
    Lexicon Pharmaceut, The Woodlands, TX USA.
    Pavel, M.
    Friedrich Alexander Univ, Erlangen, Germany.
    Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Two Phase 3 Studies in Carcinoid Syndrome2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 224-224Artikkel i tidsskrift (Annet vitenskapelig)
  • 32.
    Ebeling-Barbier, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Garske-Roman, Ulrike
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Antonodimitrakis, Pantelis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Radioembolization with 90Y-Labelled Resin Microspheres in Patients with Liver Metastases from Neuroendocrine Tumors2015Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, nr 1-2, s. 136-137Artikkel i tidsskrift (Annet vitenskapelig)
  • 33.
    Edfeldt, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Daskalakis, Kosmas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bäcklin, Christofer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    DcR3, TFF3 and Midkine are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 2, s. 170-181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are amine- and peptide producing neoplasms. Most patients display metastases at the time of diagnosis, they have an unpredictable individual disease course and the tumors are often therapy resistant. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are the clinically most used biomarkers today, but there is a great need for novel diagnostic and prognostic biomarkers and new therapeutic targets. Sixty-nine biomarkers were screened in serum from 23 SI-NET patients and 23 healthy controls using multiplex PLA (proximity ligation assay). A refined method, PEA (proximity extension assay), was used to analyze 76 additional biomarkers. Statistical testing and multivariate classification were performed. Immunohistochemistry and ELISA assays were performed in an extended cohort. Using PLA, 19 biomarkers showed a significant difference in serum concentrations between patients and controls, and PEA revealed difference in concentrations in 13 proteins. Multivariate classification analysis revealed decoy receptor 3 (DcR3), trefoil factor 3 (TFF3) and Midkine to be good biomarkers for disease, which was confirmed by ELISA analysis. All three biomarkers were expressed in tumor tissue. DcR3 concentrations were elevated in patients with stage IV disease. High concentrations of DcR3 and TFF3 were correlated to poor survival. DcR3, TFF3 and Midkine exhibited elevated serum concentrations in SI-NET patients compared to healthy controls, and DcR3 and TFF3 were associated with poor survival. DcR3 seems to be a marker for liver metastases while TFF3 and Midkine may be new diagnostic biomarkers for SI-NETs.

  • 34.
    Edfeldt, Katarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stalberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    ACTG2 Inhibits Growth and Is Epigenetically Repressed in Small Intestinal Neuroendocrine Tumors2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, nr 3-4, s. 227-227Artikkel i tidsskrift (Annet vitenskapelig)
  • 35.
    Eriksson, Barbro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Annibale, Bruno
    Bajetta, Emilio
    Mitry, Emmanuel
    Pavel, Marianne
    Platania, Marco
    Salazar, Ramon
    Ploeckinger, Ursula
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Chemotherapy in Patients with Neuroendocrine Tumors2009Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 90, nr 2, s. 214-219Artikkel i tidsskrift (Fagfellevurdert)
  • 36.
    Eriksson, Barbro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Klöppel, Günter
    Krenning, Eric
    Ahlman, Håkan
    Plöckinger, Ursula
    Wiedenmann, Bertram
    Arnold, Rudolf
    Auernhammer, Christoph
    Körner, Meike
    Rindi, Guido
    Wildi, Stefan
    Consensus guidelines for the management of patients with digestive neuroendocrine tumors: well-differentiated jejunal-ileal tumor/carcinoma2008Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 87, nr 1, s. 8-19Artikkel i tidsskrift (Fagfellevurdert)
  • 37.
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Virotherapy of Neuroendocrine Tumors2013Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 97, nr 1, s. 26-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most patients with small intestinal neuroendocrine tumors (SI-NETs), also referred to as midgut carcinoids, present with systemic disease at the time of diagnosis with metastases primarily found in regional lymph nodes and the liver. Curative treatment is not available for these patients and there is a need for novel and specific therapies. Engineered oncolytic viruses may meet the need and play an important role in the future management of SI-NET liver metastases. This review focuses on adenovirus as the oncolytic anti-cancer agent and its potential curative role for SI-NET liver metastases, but it also summarizes the use of oncolytic viruses for NETs in general. It discusses how specific features of neuroendocrine cell biology can be used to engineer viruses to become selective for infection of NET cells and/or replication within NET cells. In addition, it points out the advantages and shortcomings of using replicating viruses in the treatment of cancer and addresses research fields that can increase the efficacy of virus-based therapy.

  • 38.
    Falconi, M.
    et al.
    Univ Vita & Salute, Hosp San Raffaele, Dept Surg, Milan, Italy..
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Kaltsas, G.
    Natl Univ Athens, Div Endocrinol, Dept Pathophysiol, Athens, Greece..
    Bartsch, D. K.
    Univ Marburg, Dept Surg, Marburg, Germany..
    Capdevila, J.
    Vall dHebron Univ Hosp, Inst Oncol VHIO, Barcelona, Spain..
    Caplin, M.
    Royal Free Hosp, Neuroendocrine Tumour Unit, Pond St, London NW3 2QG, England..
    Kos-Kudla, B.
    Med Univ Silesia, Dept Endocrinol, Katowice, Poland..
    Kwekkeboom, D.
    Erasmus MC, Div Nucl Med, Dept Internal Med, Rotterdam, Netherlands..
    Rindi, G.
    Univ Cattolica Sacro Cuore, Policlin A Gemelli, Inst Pathol Anat, Rome, Italy..
    Kloeppel, G.
    Tech Univ Munich, Inst Pathol, D-80290 Munich, Germany..
    Reed, N.
    Gartnavel Royal Hosp, Beatson Oncol Ctr, Glasgow, Lanark, Scotland..
    Kianmanesh, R.
    CHU Robert Debre, Dept Surg, Reims, France..
    Jensen, R. T.
    NIH, Digest Dis Branch, Bldg 10, Bethesda, MD 20892 USA..
    ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, nr 2, s. 153-171Artikkel i tidsskrift (Fagfellevurdert)
  • 39. Falconi, Massimo
    et al.
    Bartsch, Detlef Klaus
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Klöppel, Günter
    Lopes, Josém
    O'Connor, Juan M
    Salazar, Ramón
    Taal, Babs G
    Vullierme, Marie Pierre
    O'Toole, Dermot
    ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms of the Digestive System: Well-Differentiated Pancreatic Non-Functioning Tumors2012Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 95, nr 2, s. 120-134Artikkel i tidsskrift (Fagfellevurdert)
  • 40. Falconi, Massimo
    et al.
    Plockinger, Ursula
    Kwekkeboom, Dik J.
    Manfredi, Riccardo
    Korner, Meike
    Kvols, Larry
    Pape, Ulrich F.
    Ricke, Jens
    Goretzki, Peter E.
    Wildi, Stefan
    Steinmuller, Thomas
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Scoazec, Jean-Yves
    Well-differentiated pancreatic nonfunctioning tumors/carcinoma2006Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 84, nr 3, s. 196-211Artikkel i tidsskrift (Fagfellevurdert)
  • 41.
    Fjällskog, Marie-Louise H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Janson, Eva Tiensuu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Falkmer, Ursula G.
    Vatn, Morten H.
    Öberg, Kjell E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Barbro K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors2008Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 88, nr 1, s. 53-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 42.
    Galleberg, R. B.
    et al.
    Haukeland Hosp, Dept Oncol, Bergen, Norway..
    Knigge, U.
    Univ Copenhagen, Rigshosp, Dept Surg & Endocrinol PE C, Copenhagen, Denmark..
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Vestermark, L. W.
    Odense Univ Hosp, Dept Oncol, Odense, Denmark..
    Haugvik, S. P.
    Oslo Univ Hosp, Rikshosp, Dept Hepatopancreatobiliary Surg 5, Oslo, Norway..
    Ladekarl, M.
    Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark..
    Langer, S. W.
    Univ Copenhagen, Rigshosp, Dept Oncol 7, Copenhagen, Denmark..
    Gronbaek, H.
    Aarhus Univ Hosp, Dept Hepatol & Gastroenterol 8, Aarhus, Denmark..
    Osterlund, P.
    Univ Helsinki, Cent Hosp, Dept Oncol 9, Helsinki, Finland..
    Hjortland, G.
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Assmus, J.
    Haukeland Hosp, Ctr Clin Res 11, Bergen, Norway..
    Tang, L.
    MSKCC, Dept Pathol, New York, NY USA..
    Perren, A.
    Univ Bern, Dept Pathol, Bern, Switzerland..
    Sorbye, H.
    Haukeland Hosp, Dept Oncol, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Resection of Liver Metastases in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Carcinomas: A Nordic Multicenter Study2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 264-264Artikkel i tidsskrift (Annet vitenskapelig)
  • 43.
    Garcia-Carbonero, Rocio
    et al.
    Univ Complutense, CNIO, Hosp Univ Doce Octubre, Med Oncol Dept.
    Rinke, Anja
    Univ Hosp Marburg UKGM, Div Gastroenterol & Endocrinol.
    Valle, Juan W.
    Univ Manchester, Inst Canc Sci, Christie NHS Fdn Trust, Dept Med Oncol, Manchester.
    Fazio, Nicola
    European Inst Oncol, Unit Gastrointestinal Med Oncol & Neuroendocrine.
    Caplin, Martyn
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Gorbounova, Vera
    Inst Russian Acad Med Sci, Dept Oncol.
    O'Connor, Juan
    Inst Alexander Fleming, Dept Clin Oncol, Buenos Aires.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol.
    Kulke, Matthew
    Harvard Med Sch, Dana Farber Canc Inst.
    Chen, Jie
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou.
    Falkerby, Jenny
    Uppsala Univ Hosp, Dept Endocrine Oncol.
    Costa, Frederico
    Hosp Sirio Libanes.
    de Herder, Wouter
    Erasmus MC, ENETS Ctr Excellence Rotterdam, Div Endocrinol, Dept Internal Med.
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Med Oncol Dept.
    Pavel, Marianne
    Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Gastroenterol & Hepatol.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Chemotherapy2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 3, s. 281-294Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systemic chemotherapy is indicated in progressive or bulky advanced pancreatic neuroendocrine tumors (NETs) and in grade 3 (G3) neuroendocrine neoplasms (NENs) as per ENETS guidelines. Chemotherapy may be considered in NETs of other sites (lung, thymus, stomach, colon, and rectum) under certain conditions (e.g., when Ki-67 is at a high level [upper G2 range], in rapidly progressive disease and/or after failure of other therapies, or if somatostatin receptor imaging is negative). An ENETS Consensus Conference was held in Antibes (2015) to elaborate guidelines on the standards of care of different diagnostic procedures and therapeutic interventions in NENs. This article provides guidance on chemotherapy including therapeutic indications, dosing schedules, adverse events (including prevention and management), drug interactions, and evaluation of treatment effect for the chemotherapy agents most commonly used in NENs (streptozocin, dacarbazine, fluoropyrimidines, platinum compounds, etoposide, and irinotecan).

  • 44.
    Giandomenico, V
    et al.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    Li, Su-Chen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Boccherini, M.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ Hosp, Uppsala, Sweden..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ Hosp, Uppsala, Sweden..
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Paganelli, G.
    IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, FC, Italy..
    miR-196a Is Specifically Regulated in FDG-PET Positive and Negative Small Intestinal Neuroendocrine Tumor Patients at Late Stage of Disease2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 115-115Artikkel i tidsskrift (Fagfellevurdert)
  • 45.
    Giandomenico, Valeria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Modlin, Irvin M.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Nilsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Khan, Mohid S.
    Millar, Robert P.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Borlak, Jurgen
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Nielsen, Bengt
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Waterton, John C.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Improving the Diagnosis and Management of Neuroendocrine Tumors: Utilizing New Advances in Biomarker and Molecular Imaging Science2013Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 98, nr 1, s. 16-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Oberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.

  • 46. Glasberg, S.
    et al.
    Thomas, D.
    Strosberg, J. R.
    Pape, U. F.
    Felder, S.
    Tsolakis, Apostolos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Alexandraki, K.
    Fraenkel, M.
    Saiegh, L.
    Reissman, P.
    Kaltsas, G.
    Gross, D. J.
    Metastatic Type 1 Gastric Carcinoid-A Real Threat or Just a Myth?2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 99, nr 3-4, s. 302-302Artikkel i tidsskrift (Annet vitenskapelig)
  • 47.
    Grönberg, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Tsolakis, Apostolos V
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Holmbäck, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Janson, Eva T
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake2013Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 97, nr 4, s. 291-299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs.

    Materials and Methods:

    The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs.

    Results:

    Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals.

    Conclusion:

    Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.

    Fulltekst (pdf)
    fulltext
  • 48.
    Grönbladh, Alfhild
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Johansson, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nyberg, Fred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Hallberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Recombinant Human Growth Hormone Affects the Density and Functionality of GABAB receptors in the Male Rat Brain2013Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 97, nr 3, s. 203-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The beneficial effects of growth hormone (GH) on memory and learning have previously been confirmed in both humans and in animal models. An important role of GABA(B) receptors for multiple forms of learning and memory has also been reported. In this study, we examined the effect of GH on the density and functionality of the metabotropic GABA(B) receptors in the rat brain. Male Sprague-Dawley rats (n = 24) divided into 3 groups were injected twice daily with recombinant human GH (0.07 or 0.7 IU/kg) for 7 days. The effects of the hormone were determined by quantitative autoradiography and by GABA(B) stimulated [(35)S]-GTPγS binding using the selective GABA(B) receptor agonist baclofen. The results demonstrate moderate but significant alterations in both receptor density and functionality in a number of brain regions. For example, a dose-dependent upregulation of GABA(B) receptors was found in the cingulate cortex, primary motor cortex and caudate putamen, whereas attenuation in the receptor density was encountered in, for example, the medial geniculate nucleus. Although the GH-induced effects on the GABA(B) receptor in brain areas associated with cognition were fairly pronounced, they were significant and we propose that the physiological responses observed after GH administration at least partly can be mediated through a mechanism involving GABA(B) receptors.

  • 49.
    Hicks, Rodney J.
    et al.
    Peter MacCallum Canc Ctr, Canc Imaging & Neuroendocrine Serv, 305 Grattan St.
    Kwekkeboom, Dik J.
    Erasmus MC, ENETS Ctr Excellence Rotterdam, Div Nucl Med, Dept Internal Med.
    Krenning, Eric
    Erasmus MC, Cyclotron Rotterdam BV.
    Bodei, Lisa
    Mem Sloan Kettering Canc Ctr.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Med Ctr, Neuroendocrine Tumor Unit, Endocrinol & Metab Serv,Dept Med.
    Arnold, Rudolf
    Munich, Germany.
    Borbath, Ivan
    Clin Univ St Luc, Serv Gastroenterol.
    Cwikla, Jaroslaw
    Univ Warmia & Mazury, Dept Radiol, Fac Med Sci.
    Toumpanakis, Christos
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Kaltsas, Greg
    Natl Univ Athens, Div Endocrinol, Dept Pathophysiol.
    Davies, Philippa
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Hoersch, Dieter
    Gastroenterol & Endocrinol Ctr Neuroendocrine Tum.
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Ramage, John
    Hampshire Hosp NHS Trust, Gastroenterol Dept, Basingstoke.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 3, s. 295-309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish Lu-177-DOTA-octreotate (LutaThera (R)) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

  • 50.
    Hrsch, D.
    et al.
    Zent Klin Bad Berka, Bad Berka, Germany..
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Caplin, M.
    Royal Free Hosp, London, England..
    Anthony, L.
    Univ Kentucky, Lexington, KY 40506 USA..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Warner, R.
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Lombard-Bohas, C.
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Kunz, P.
    Stanford Univ, Palo Alto, CA 94304 USA..
    Valle, J.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England..
    Fleming, D.
    Ipsen BioSci, Cambridge, MA USA..
    Lapuerta, P.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Banks, P.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Pavel, M.
    Charite, Berlin, Germany..
    Efficacy and Safety of Telotristat Etiprate in Patients with Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog Therapy: Analysis of the Ongoing TELESTAR Extension Period2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 88-88Artikkel i tidsskrift (Fagfellevurdert)
123 1 - 50 of 121
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