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  • 1.
    Ahlin, Cecilia
    et al.
    Orebro Univ, Dept Oncol, Orebro, Sweden..
    Lundgren, Claudia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Embretsen-Varro, Elin
    Orebro Univ, Dept Oncol, Orebro, Sweden..
    Jirstrom, Karin
    Lund Univ, Dept Pathol & Oncol, Lund, Sweden..
    Blomqvist, Carl
    Orebro Univ, Dept Oncol, Orebro, Sweden.;Univ Helsinki, Dept Oncol, Helsinki, Finland..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers2017In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 164, no 3, p. 667-678Article in journal (Refereed)
    Abstract [en]

    Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.

  • 2.
    Ali, Abir A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Grönberg, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Intravenous versus Oral Etoposide: Efficacy and Correlation to Clinical Outcome in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 184-184Article in journal (Other academic)
  • 3.
    Ali, Abir Salwa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Grönberg, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Federspiel, Birgitte
    Rigshosp, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Scoazec, Jean-Yves
    Inst Gustave Roussy, Villejuif, France.
    Hjortland, Geir Olav
    Univ Oslo, Oslo, Norway.
    Gronbaek, Henning
    Aarhus Univ Hosp, Aarhus, Denmark.
    Ladekarl, Morten
    Aarhus Univ Hosp, Aarhus, Denmark.
    Langer, Seppo W.
    Rigshosp, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Vestermark, Lene Weber
    Odense Univ Hosp, Odense, Denmark.
    Arola, Johanna
    Univ Helsinki, Helsinki, Finland; Helsinki Univ Hosp, Helsinki, Finland.
    Osterlund, Pia
    Univ Helsinki, Helsinki, Finland; Helsinki Univ Hosp, Helsinki, Finland; Tampere Univ Hosp, Tampere, Finland.
    Knigge, Ulrich
    Univ Copenhagen, Rigshosp, Copenhagen, Denmark.
    Sorbye, Halfdan
    Haukeland Hosp, Bergen, Norway; Univ Bergen, Bergen, Norway.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology. Uppsala Univ, Sect Endocrine Oncol, Dept Med Sci, Uppsala, Sweden..
    Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0187667Article in journal (Refereed)
    Abstract [en]

    Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

  • 4.
    Ali, Abir Salwa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Grönberg, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Langer, Seppo W.
    Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Surg C, Copenhagen, Denmark.;Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Endocrinol PE, Copenhagen, Denmark.;Rigshosp, Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark..
    Ladekarl, Morten
    Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark..
    Hjortland, Geir Olav
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Vestermark, Lene Weber
    Odense Univ Hosp, Dept Oncol, Odense, Denmark..
    Österlund, Pia
    Tampere Univ Hosp, Dept Oncol, Tampere, Finland.;Tampere Univ, Tampere, Finland.;Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Gronbaek, Henning
    Aarhus Univ Hosp, Dept Hepatol, Aarhus, Denmark.;Aarhus Univ Hosp, Dept Gastroenterol, Aarhus, Denmark..
    Knigge, Ulrich
    Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Surg C, Copenhagen, Denmark.;Univ Copenhagen, Rigshosp, Fac Hlth Sci, Dept Endocrinol PE, Copenhagen, Denmark.;Rigshosp, Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark..
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway..
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Intravenous versus oral etoposide: efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)2018In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 35, no 4, article id 47Article in journal (Refereed)
    Abstract [en]

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.

  • 5.
    Almquist, M.
    et al.
    Skane Univ Hosp, Dept Surg, Lund, Sweden..
    Myrenfors, P.
    IPSEN, Stockholm, Sweden..
    Strom, T.
    IPSEN, Stockholm, Sweden..
    Kozlovacki, Gordana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    STREET - Somatostatin Treatment Experience Trial2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, p. 191-191Article in journal (Other academic)
  • 6.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 Syndrome2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, p. 212-212Article in journal (Other academic)
  • 7.
    Antonodimitrakis, Pantelis Clewemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Olofsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study2017In: International Journal of Endocrine Oncology, Vol. 4, no 1, p. 9-22Article in journal (Refereed)
    Abstract [en]

    Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

  • 8.
    Antonodimitrakis, Pantelis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 3-4, p. 345-353Article in journal (Refereed)
    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.

  • 9.
    Bjorstad, A.
    et al.
    Nord Hlth Econ, Gothenburg, Sweden..
    Marlow, T.
    Nord Hlth Econ, Gothenburg, Sweden..
    Lesen, E.
    Nord Hlth Econ, Gothenburg, Sweden..
    Bollano, E.
    Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Marteau, F.
    Ipsen Pharma, Boulogne, France..
    Gabriel, S.
    Ipsen Pharma, Boulogne, France..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Fcuilly, M.
    Ipsen Pharma, Boulogne, France..
    Real-World Resource Use And Costs Of Carcinoid Heart Disease In Patients With Neuroendocrine Tumors: A Retrospective Swedish Study2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A552-A552Article in journal (Other academic)
  • 10.
    Borjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nurses’ experiences of taxane-induced pain in people treated for breast cancerIn: Article in journal (Other academic)
  • 11.
    Börjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Centrum för klinisk forskning, Falun.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Rissanen, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Colored body images reveal the perceived intensity anddistribution of pain in women with breast cancer treated withadjuvant taxanes:: a prospective multi-method study of painexperience2018In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Scand J Pain, ISSN ISSN 1877-8860, p. 1-11, article id https://doi.org/10.1515/sjpain-2018-0050Article, review/survey (Refereed)
    Abstract [en]

    Background and aims:

    Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients’ pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study.

    Methods:

    Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire’s (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months.

    Results:

    Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30.

    Conclusions:

    This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain.

    Implications:

    Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24–48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.

  • 12.
    Casar Borota, Olivera
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Stigare, Jerker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Boldt, Henning Bünsow
    Kristensen, Bjarne Winther
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Trouillas, Jacqueline
    Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.2017In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 41, no 9, p. 1238-1246Article in journal (Refereed)
    Abstract [en]

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  • 13.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumors2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, p. 441-441Article in journal (Other academic)
  • 14.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    A Prospective Nordic Study on the Use of Chromogranin A for the Prediction of Progression in Patients with Pancreatic and Small Intestinal Neuroendocrine Tumors2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 152-152Article in journal (Other academic)
  • 15.
    Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Karakatsanis, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stuart, Heather C.
    Division of Surgical Oncology, University of Miami, Florida, USA.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Association of a Prophylactic surgical approach to Stage IV Small Intestinal Neuroendocrine Tumors with Survival.2018In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 2, p. 183-189Article in journal (Refereed)
    Abstract [en]

    Importance: Primary tumor resection and mesenteric lymph node dissection in asymptomatic patients with stage IV Small Intestinal Neuroendocrine Tumors (SI-NETs) is controversial.

    Objective:  To determine whether locoregional surgery performed at diagnosis in asymptomatic SI-NETs patients with distant metastases affects overall survival (OS), morbidity and mortality, length of hospital stay (LOS) and re-operation rates.

    Design: This investigation was a cohort study of asymptomatic patients with stage IV SI-NET, diagnosed between 1985 and 2015, using the prospective Uppsala database of SI-NETs and the Swedish National Patient Register. Patients included were followed until May 2016 and divided to a first group, which underwent Prophylactic Upfront Surgery within six months from diagnosis Combined with Oncological treatment (PUSCO group) and a second group, which was either treated non-surgically or operated later (Delayed Surgery As Needed Combined with Oncological treatment [DSANCO group]).

    Setting: A tertiary referral center with follow-up data from the Swedish National Patient Register.

    Participants: We included 363 stage IV SI-NET patients without any abdominal symptoms within 6 months from diagnosis, treated either with PUSCO (n=161) or DSANCO (n=202).

    Exposure: PUSCO vs DSANCO.

    Main Outcomes and Measures: Overall survival (OS), length of hospital stay (LOS), postoperative morbidity and mortality and re-operation rates measured from baseline. Propensity score match was performed between the two groups.

    Results: Two isonumerical groups (n=91) occurred after propensity score matching. There was no difference between groups in OS (PUSCO median 7.9 vs DSANCO 7.6 years; [hazard ratio] HR, 0.98; [95% CI, 0.70-1.37]; log-rank P=.93) and cancer-specific survival (median 7.7 vs 7.6 years, HR, 0.99; [95%CI, 0.71-1.40]; log-rank P=.99). There was no difference in 30-day mortality (0% in both matched groups) or postoperative morbidity (2% vs 1%; P>.99), LOS (median 73 vs 76 days; P=.64), LOS due to local tumor-related symptoms (median 7 vs 11.5 days; P=.81) or incisional hernia repairs (4% in both groups; P>.99).  Patients from the PUSCO group underwent more re-operative procedures (14%) compared to the DSANCO group (3%) due to intestinal obstruction (P< .001).

    Conclusion: Prophylactic upfront locoregional surgery confers no survival advantage in asymptomatic stage IV SI-NET patients. Delayed surgery as needed seems to be comparable in all examined outcomes, whilst offering the advantage of less re-operations for intestinal obstruction.  The value of a priori locoregional surgery in the presence of distant metastases is challenged and needs to be elucidated in a randomized controlled study.

     

  • 16.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 Syndrome2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 224-224Article in journal (Other academic)
  • 17.
    Dillon, Joseph S.
    et al.
    Univ Iowa, Iowa City, IA USA.
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA USA.
    Pavel, Marianne
    Charite, Berlin, Germany; Friedrich Alexander Univ, Nurnberg, Germany.
    Horsch, Dieter
    Zent Klin Bad Berka, Bad Berka, Germany.
    Anthony, Lowell B.
    Univ Kentucky, Lexington, KY USA.
    Warner, Richard R. P.
    Icahn Sch Med Mt Sinai, New York, NY USA.
    Bergsland, Emily
    Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    O'Dorisio, Thomas M.
    Univ Iowa, Iowa City, IA USA.
    Patel, Nilay
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Time to Sustained Improvement in Bowel Movement Frequency With Telotristat Ethyl: Analysis of the Phase 3 TELESTAR Study2018In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 47, no 3, p. 337-338Article in journal (Other academic)
  • 18.
    Dumanski, Jan P.
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Rasi, Chiara
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Davies, Hanna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ali, Abir S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Grönberg, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Sorbye, Halfdan
    Grønbæk, Henning
    Cunningham, Janet L
    Forsberg, Lars A.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors2017In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 24, no 8, p. 427-443Article in journal (Refereed)
    Abstract [en]

    The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.

  • 19.
    Edfeldt, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Daskalakis, Kosmas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bäcklin, Christofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    DcR3, TFF3 and Midkine are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 2, p. 170-181Article in journal (Refereed)
    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.

  • 20.
    Fust, K.
    et al.
    Optum, Boston, MA USA..
    Maschio, M.
    Optum, Burlington, ON, Canada..
    Pastor, M.
    Optum, Burlington, ON, Canada..
    Kohli, M.
    Optum, Burlington, ON, Canada..
    Weinstein, M. C.
    Harvard TH Chan Sch Publ Hlth, Boston, MA USA..
    Singh, S.
    Sunnybrook Res Inst, Toronto, ON, Canada..
    Pritchard, M.
    Univ Liverpool, Liverpool, Merseyside, England..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Marteau, R.
    Ipsen Pharma, Boulogne, France..
    Gabriel, S.
    Ipsen Pharma, Boulogne, France..
    Feuilly, M.
    Ipsen Pharma, Boulogne, France..
    A Budget Impact Model Of The Addition Of Telotristat Ethyl Treatment In Patients With Uncontrolled Carcinoid Syndrome2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A548-A549Article in journal (Other academic)
  • 21.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 Study2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, p. 264-264Article in journal (Other academic)
  • 22.
    Galleberg, R. B.
    et al.
    Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway..
    Knigge, U.
    Univ Copenhagen, Dept Surg C, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Dept Endocrinol PE, Rigshosp, Copenhagen, Denmark..
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Vestermark, L. W.
    Odense Univ Hosp, Dept Oncol, Odense, Denmark..
    Haugvik, S. -P
    Ladekarl, M.
    Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark..
    Langer, S. W.
    Univ Copenhagen, Dept Oncol, Rigshosp, Copenhagen, Denmark..
    Gronbaek, H.
    Aarhus Univ Hosp, Dept Hepatol & Gastroenterol, Aarhus, Denmark..
    Osterlund, P.
    Univ Helsinki, Dept Oncol, Cent Hosp, Helsinki, Finland..
    Hjortland, G. O.
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Assmus, J.
    Haukeland Hosp, Ctr Clin Res, 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, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 9, p. 1682-1689Article in journal (Refereed)
    Abstract [en]

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan Meier analyses for the entire cohort and for subgroups. Results: Median OS after resection/RFA of liver metastases was 35.9 months (95% -CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95% -CI: 3.9-13). Four patients (13%) were disease -free after 5 years. Two patients had well -differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 >= 55%. A Ki-67 < 55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA. Conclusion: This study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.

  • 23.
    Garske, Ulrike
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fröss-Baron, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lundin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no 6, p. 970-988Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.

    METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).

    RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.

    CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

  • 24.
    Georgantzi, Kleopatra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Sköldenberg, Erik G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Jakobson, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Christofferson, Rolf H B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Diagnostic Ultrasound-Guided Cutting Needle Biopsies in Neuroblastoma: a safe and efficient procedureManuscript (preprint) (Other academic)
  • 25.
    Georgantzi, Kleopatra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. University Children's Hospital, Uppsala, Sweden.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery. University Children's Hospital, Uppsala, Sweden.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology. University Hospital, Uppsala, Sweden.
    Kogner, Per
    Department of Women´s and Children´s Health, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Jakobson, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. University Children's Hospital, Uppsala, Sweden.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Christofferson, Rolf. H.B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery. University Children's Hospital, Uppsala, Sweden.
    Chromogranin A and neuron-specific enolase in neuroblastoma: Correlation to stage and prognostic factors.2018In: Pediatric Hematology & Oncology, ISSN 0888-0018, E-ISSN 1521-0669, Vol. 35, no 2, p. 156-165Article in journal (Refereed)
    Abstract [en]

    Chromogranin A (CgA) and neuron specific enolase (NSE) are important markers in adult neuroendocrine tumors (NET). Neuroblastoma (NB) has certain neuroendocrine properties. The aim of this study was to correlate blood concentrations of CgA, chromogranin B (CgB), and NSE to prognostic factors and outcome in children with NB. Blood samples from 92 patients with NB, 12 patients with benign ganglioneuroma (GN), 21 patients with non-NB solid tumors, 10 patients with acute leukemias, and 69 healthy children, were analyzed. CgA concentrations were higher in neonates vs. children older than one month in the control group (p < 0.0001), and in neonates with NB vs. the control group (p < 0.01). CgA and NSE concentrations were higher in patients with stages 3 and 4 disease (p < 0.05 and p < 0.05), in patients having tumors with amplification of MYCN (p < 0.05 and p < 0.001), or chromosome 1 p deletion (p < 0.05 and p < 0.05). NSE correlated to the tumor size at diagnosis (p < 0.001) and to tumor related death (p < 0.01) in NB. CgA and NSE concentrations were elevated in patients with NB and especially in those with advanced disease. Both CgA and NSE correlated to genetic markers, while only NSE correlated to primary tumor size and outcome in NB. We found that CgA and NSE are clinically valuable tumor markers in NB and they merit prospective clinical evaluations as such.

  • 26.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ahlin, Cecilia
    Orebro Univ, Fac Med & Hlth, Dept Oncol, Orebro, Sweden..
    Naeser, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176059Article in journal (Refereed)
    Abstract [en]

    Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size <= 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

  • 27.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Nilsson, Cecilia
    Vastmanland Cty Hosp, Ctr Clin Res, Vasteras, Sweden.
    Markholm, Ida
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Hedenfalk, Ingrid
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Blomqvist, Carl
    Univ Helsinki, Dept Oncol, Helsinki, Finland;Orebro Univ Hosp, Dept Oncol, Orebro, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ghrelin expression is associated with a favorable outcome in male breast cancer2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 13586Article in journal (Refereed)
    Abstract [en]

    Ghrelin and obestatin are two gastrointestinal peptides, derived from a common precursor. Expression of both peptides have been found in breast cancer tissue and ghrelin has been associated with breast cancer development. Ghrelin expression is associated with longer survival in women diagnosed with invasive and node negative breast cancer. The clinical implications of the peptide expression in male breast cancer are unclear. The aim of this study was to investigate the role and potential clinical value of ghrelin and obestatin in male breast cancer. A tissue microarray of invasive male breast cancer specimens from 197 patients was immunostained with antibodies versus the two peptides. The expression of the peptides was correlated to previously known prognostic factors in breast cancer and to the outcome. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was statistically significantly correlated to breast cancer-specific survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic factor for breast cancer death in male breast cancer. Patients with tumors expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those lacking ghrelin expression. Drugs targeting ghrelin are currently being investigated in clinical studies treating metabolic or nutritional disorders. Ghrelin should be further evaluated in forthcoming studies as a prognostic marker with the aim to be included in decision algorithms.

  • 28.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    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 Analogues2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 295-309Article in journal (Refereed)
    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.

  • 29.
    Humphries, Matthew P.
    et al.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Rajan, Sreekumar Sundara
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Droop, Alastair
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.;Univ Leeds, MRC Med Bioinformat Ctr, Leeds, W Yorkshire, England..
    Suleman, Charlotte A. B.
    St James Univ Hosp, Dept Histopathol, Leeds, W Yorkshire, England..
    Carbone, Carmine
    Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy..
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Honarpisheh, Hedieh
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Cserni, Gabor
    Bacs Kiskun Cty Teaching Hosp, Dept Pathol, Kecskemet, Hungary..
    Dent, Jo
    Calderdale Hosp, Halifax, England..
    Fulford, Laura
    Surrey & Sussex NHS Trust, Redhill, Surrey, England..
    Jordan, Lee B.
    Univ Dundee, NHS Tayside, Dundee, Scotland..
    Jones, J. Louise
    Barts Canc Inst, London, England..
    Kanthan, Rani
    Univ Saskatchewan, Dept Pathol & Lab Med, Saskatoon, SK, Canada..
    Litwiniuk, Maria
    Poznan Univ Med Sci, Greater Poland Canc Ctr, Poznan, Poland..
    Di Benedetto, Anna
    Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy..
    Mottolese, Marcella
    Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy..
    Provenzano, Elena
    Addenbrookes Hosp, Dept Histopathol, Cambridge, England..
    Shousha, Sami
    Imperial Coll Healthcare NHS Trust, Dept Histopathol, London, England.;Charing Cross Hosp, Imperial Coll, London, England..
    Stephens, Mark
    Univ Hosp North Staffordshire, Stoke On Trent, Staffs, England..
    Walker, Rosemary A.
    Univ Leicester, Canc Studies & Mol Med, Leicester, Leics, England..
    Kulka, Janina
    Semmelweis Univ, Dept Pathol 2, Budapest, Hungary..
    Ellis, Ian O.
    Nottingham City Hosp, Fac Med & Hlth Sci, Nottingham, England..
    Jeffery, Margaret
    Queen Alexandra Hosp, Pathol Ctr, Dept Histopathol, Portsmouth, Hants, England..
    Thygesen, Helene H.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Cappelletti, Vera
    Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy..
    Daidone, Maria G.
    Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy..
    Hedenfalk, Ingrid A.
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Melisi, Davide
    Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy.;Univ Verona, Dept Med, Digest Mol Clin Oncol Res Unit, Verona, Italy..
    Stead, Lucy F.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Shaaban, Abeer M.
    Queen Elizabeth Hosp Birmingham, Dept Cellular Pathol, Birmingham, W Midlands, England.;Univ Birmingham, Birmingham, W Midlands, England..
    Speirs, Valerie
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 10, p. 2575-2583Article in journal (Refereed)
    Abstract [en]

    Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.

    Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.

    Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [ eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.

    Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

  • 30. Jensen, Robert T
    et al.
    Bodei, Lisa
    Capdevila, J
    Couvelard, Anne
    Falconi, Massimo
    Grozinsky-Glasberg, Simona
    Klöppel, Günter
    Lamberts, Steven W J
    Peeters, Marc
    Rindi, Guido
    Rinke, Anja
    Rothmund, M
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Fazio, Nicola
    Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine neoplasms2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194Article in journal (Refereed)
    Abstract [en]

    Recently, European Neuroendocrine Tumor Society (ENETS )held working sessions composed of members of the advisory board and other Neuroendocrine neoplasms (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This section briefly summarizes the main proposed areas of unmet needs in patients with functional and non-functional pancreatic neuroendocrine neoplasms (PanNENs).

  • 31.
    Kaltsas, Gregory
    et al.
    Univ Athens, Dept Pathophysiol, Endocrine Unit.
    Caplin, Martyn
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Davies, Philippa
    Royal Free Hosp, Neuroendocrine Tumour Unit.
    Ferone, Diego
    Univ Genoa, IRCCS AOU San Martino IST, Dept Internal Med & Med Specialties DiMI, Endocrinol Unit, CEBR.
    Garcia-Carbonero, Rocio
    Hosp Univ Doce Octubre, Med Oncol Dept.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Neuroendocrine Unit.
    Hoersch, Dieter
    Gastroenterol & Endocrinol Ctr Neuroendocrine Tum.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Kianmanesh, Reza
    Robert Debre Hosp, Dept Digest & Endocrine Surg.
    Kos-Kudla, Beata
    Med Univ Silesia, Div Endocrinol, Dept Pathophysiol & Endocrinol.
    Pavel, Marianne
    Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Hepatol & Gastroenterol.
    Rinke, Anja
    UKGM Marburg, Dept Gastroenterol.;Philipps Univ Marburg.
    Falconi, Massimo
    Univ Vita & Salute, Osped San Raffaele, Pancreas Translat & Clin Res Ctr, Chirurg Pancreas.
    de Herder, Wouter W.
    Erasmus MC Canc Ctr, ENETS Ctr Excellence.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Pre- and Perioperative Therapy in Patients with Neuroendocrine Tumors2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 245-254Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumors of the small intestine are the most common causes of the carcinoid syndrome. Carcinoid heart disease occurs in more than half of the patients with the carcinoid syndrome. Patients with carcinoid heart disease who need to undergo surgery should also undergo preoperative evaluation by an expert cardiologist. Treatment with longacting somatostatin analogs aims at controlling the excessive hormonal output and symptoms related to the carcinoid syndrome and at preventing a carcinoid crisis during interventions. Patients with a gastrinoma require pre- and postoperative treatment with high doses of proton pump inhibitors. Patients with a glucagonoma require somatostatin analog treatment and nutritional supplementation. Patients with a VIPoma also require somatostatin analog treatment and intravenous fluid and electrolyte therapy. Insulinoma patients generally require intravenous glucose infusion prior to operation. In patients with localized operable insulinoma, somatostatin analog infusion should only be considered after the effect of this therapy has been electively studied.

  • 32.
    Khan, Tanweera Shaheena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    11C-metomidate PET imaging of adrenocortical cancer2003In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070 (Paper) 1619-7089 (Online), Vol. 30, no 3, p. 403-410Article in journal (Refereed)
  • 33.
    Kjellman, M.
    et al.
    Karolinska Hosp, Stockholm, Sweden..
    Knigge, U.
    Rigshosp, Copenhagen, Denmark..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Gronbaek, H.
    Aarhus Univ Hosp, Aarhus, Denmark..
    This-Evensen, E.
    Oslo Univ Hosp, Oslo, Norway..
    Sorbye, H.
    Haukeland Hosp, Bergen, Norway..
    Jorgensen, Thyregod M.
    Odense Univ Hosp, Odense, Denmark..
    Johanson, V
    Sahlgrenska Hosp Gothenburg, Gothenburg, Sweden..
    Strom, T.
    IPSEN Nord, Stockholm, Sweden..
    Myrenfors, P.
    IPSEN Nord, Stockholm, Sweden..
    Belusa, R.
    IPSEN Nord, Stockholm, Sweden..
    Plasma Protein Fingerprinting for the Diagnosis of Small Intestinal Neuroendocrine Tumors (siNETs)2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, p. 148-148Article in journal (Other academic)
  • 34.
    Kjellman, M.
    et al.
    Karolinska Univ Hosp, Stockholm, Sweden.
    Knigge, U.
    Rigshosp, Copenhagen, Denmark.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Grønbæk, H.
    Aarhus Univ Hosp, Aarhus, Denmark.
    Thiis-Evensen, E.
    Oslo Univ Hosp, Oslo, Norway.
    Sørbye, H.
    Haukeland Hosp, Bergen, Norway.
    Joergensen, M. T.
    Odense Univ Hosp, Odense, Denmark.
    Johanson, V.
    Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Si, Metso
    Tampere Univ Hosp, Tampere, Finland.
    Kj, Becker
    IPSEN, Stockholm, Sweden.
    Ström, T.
    IPSEN, Stockholm, Sweden.
    Belusa, R.
    IPSEN, Stockholm, Sweden.
    Plasma Protein Kallikrein-14 Strongly Predicts Pronounced Chromogranin A (CgA) Response in Small Intestinal Neuroendocrine Tumor (NET) Patients after Somatostatin Analog (SSA) Treatment: The Nordic EXPLAIN Biomarker Study2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 155-155Article in journal (Other academic)
  • 35.
    Lesen, E.
    et al.
    Nord Hlth Econ, Gothenburg, Sweden..
    Bjorstad, A.
    Nord Hlth Econ, Gothenburg, Sweden..
    Bjorholt, I
    Nord Hlth Econ, Gothenburg, Sweden..
    Feuilly, M.
    Ipsen Pharma, Boulogne, France..
    Marteau, F.
    Ipsen Pharma, Boulogne, France..
    Gabriel, S.
    Ipsen Pharma, Boulogne, France..
    Elf, A.
    Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Johanson, V
    Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Real-World Resource Use And Costs Of Treating Controlled And Uncontrolled Carcinoid Syndrome: A Retrospective Swedish Study2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A552-A552Article in journal (Other academic)
  • 36.
    Perren, Aurel
    et al.
    Univ Bern, Inst Pathol.
    Couvelard, Anne
    Hôpital Bichat Claude Bernard, Serv Pathol.
    Scoazec, Jean-Yves
    Gustave Roussy Canc Campus, Dept Biol & Pathol Med, Serv Pathol Morphol & Mol.
    Costa, Frederico
    Ctr Oncol, Sao Paulo.
    Borbath, Ivan
    Clin Univ St Luc, Serv Gastroenterol.
    Delle Fave, Gianfranco
    Osped St Andrea, Dept Digest & Liver Dis.
    Gorbounova, Vera
    Inst Russian Acad Med Sci, Dept Oncol.
    Gross, David
    Hadassah Univ Hosp, Dept Endocrinol & Metab.
    Grossman, Ashley
    Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab.
    Jensen, Robert T.
    NIH, Digest Dis Branch.
    Kulke, Matthew
    Harvard Med Sch, Dana Farber Canc Inst.
    Oberg, Kjell
    Univ Hosp, Endocrine Oncol Unit, Dept Med Sci.
    Rindi, Guido
    Univ Cattolica Sacro Cuore, Policlin A Gemelli, Inst Anat Pathol.
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Pathology-Diagnosis and Prognostic Stratification2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 196-200Article in journal (Refereed)
    Abstract [en]

    The European Neuroendocrine Tumor Society (ENETS) proposed standard of care guidelines for pathology in 2009. Since then, profound changes in the classification have been made, dividing neuroendocrine neoplasia (NEN) into well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC) in the 2010 WHO classification. The 7th edition of the TNM classification (2009) included NEN for the first time, widely adapting ENETS proposals but with some differences for NEC and for NET of the pancreas and the appendix. Therapy guidelines for gastroenteropancreatic NET were updated in 2016. The need for an update of the standards of care prompted the ENETS to organize a consensus conference which was held in Antibes in 2015; a working group was designated to propose pathological standards of care.

  • 37. Singh, Simron
    et al.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Wolin, Edward
    Warner, Richard
    Sissons, Maia
    Kolarova, Teodora
    Goldstein, Grace
    Pavel, Marianne
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Leyden, John
    Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs2017In: Journal of global oncology, ISSN 2378-9506, Vol. 3, no 1, p. 43-53Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Despite the considerable impact of neuroendocrine tumors (NETs) on patients' daily lives, the journey of the patient with a NET has rarely been documented, with published data to date being limited to small qualitative studies. NETs are heterogeneous malignancies with nonspecific symptomology, leading to extensive health care use and diagnostic delays that affect survival. A large, international patient survey was conducted to increase understanding of the experience of the patient with a NET and identify unmet needs, with the aim of improving disease awareness and care worldwide.

    METHODS: An anonymous, self-reported survey was conducted (online or on paper) from February to May 2014, recruiting patients with NETs from > 12 countries as a collaboration between the International Neuroendocrine Cancer Alliance and Novartis Pharmaceuticals. Survey questions captured information on sociodemographics, clinical characteristics, NET diagnostic experience, disease impact/management, interaction with medical teams, NET knowledge/awareness, and sources of information. This article reports the most relevant findings on patient experience with NETs and the impact of NETs on health care system resources.

    RESULTS: A total of 1,928 patients with NETs participated. A NET diagnosis had a substantially negative impact on patients' personal and work lives. Patients reported delayed diagnosis and extensive NET-related health care resource use. Patients desired improvement in many aspects of NET care, including availability of a wider range of NET-specific treatment options, better access to NET experts or specialist centers, and a more knowledgeable, better-coordinated/-aligned NET medical team.

    CONCLUSION: This global patient-reported survey demonstrates the considerable burden of NETs with regard to symptoms, work and daily life, and health care resource use, and highlights considerable unmet needs. Further intervention is required to improve the patient experience among those with NETs.

  • 38.
    Skovgaard, D.
    et al.
    Rigshosp Copenhagen, Dept Clin Physiol Nucl Med & PET, Copenhagen, Denmark.
    Fazio, N.
    European Inst Oncol, Div Gastrointestinal Med Oncol & Neuroendocrine, Milan, Italy.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Grozinsky-Glasberg, S.
    Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Dept, Neuroendocrine Tumor Unit, Jerusalem, Israel.
    Ahmadzadehfar, H.
    Univ Hosp Bonn, Dept Nucl Med, Bonn, Germany.
    Zandee, W.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Cwikla, J.
    Postgrad Med Ctr, Warsaw, Poland; Cent Clin Hosp, Warsaw, Poland.
    Walter, M.
    Univ Hosp Geneva, Nucl Med Serv, Geneva, Switzerland.
    Ringe, A.
    Philipps Univ, Dept Gastroenterol & Endocrinol, Marburg, Germany.
    Frilling, A.
    Imperial Coll London, London, England.
    Grana, C.
    European Inst Oncol, Div Gastrointestinal Med Oncol & Neuroendocrine, Milan, Italy.
    Horbye, H.
    Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Selected For Oral Presentation: Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic Grade 3 Neuroendocrine Neoplasms: A Retrospective International Multicenter Study2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 258-258Article in journal (Other academic)
  • 39.
    Weickert, Martin O.
    et al.
    Univ Hosp Coventry, ENETS Ctr Excellence, ARDEN NET Ctr, Coventry CV2 2DX, W Midlands, England;Warwickshire Natl Hlth Serv Trust, Coventry CV2 2DX, W Midlands, England.
    Kaltsas, Gregory
    Univ Hosp Coventry, ENETS Ctr Excellence, ARDEN NET Ctr, Coventry CV2 2DX, W Midlands, England;Warwickshire Natl Hlth Serv Trust, Coventry CV2 2DX, W Midlands, England.
    Hörsch, Dieter
    Zent Klin Bad Berka, Bad Berka, Germany.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Pavel, Marianne
    Friedrich Alexander Univ Erlangen Nurnberg, Erlangen, Germany;Charite, Berlin, Germany.
    Valle, Juan W.
    Univ Manchester, Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England.
    Caplin, Martyn E.
    Royal Free Hosp, European Neuroendocrine Tumor Soc Ctr Excellence, Neuroendocrine Tumour Unit, London, England.
    Bergsland, Emily
    Univ Calif San Francisco, San Francisco, CA 94143 USA.
    Kunz, Pamela L.
    Stanford Univ, Sch Med, Stanford, CA USA.
    Anthony, Lowell B.
    Univ Kentucky, Lexington, KY USA.
    Grande, Enrique
    MD Anderson Int Canc Ctr, Madrid, Spain.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France.
    Ramage, John K.
    Kings Coll Hosp London, Kings Hlth Partners European Neuroendocrine Tumor, London, England.
    Kittur, Ashwin
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Yang, Qi M.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome2018In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 40, no 6, p. 952-962Article in journal (Refereed)
    Abstract [en]

    Purpose: In the placebo-controlled Phase III TELE-STAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and >= 4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m(2)) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

    Methods: Assessment of the occurrence of weight change >= 3% at week 12 was prespecified in the statistical analysis plan.

    Findings: In 120 patients with weight data available, weight gain >= 3% was observed in 2 of 39 patients (5.1%) taking placebo [1.1), 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss >= 3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.

  • 40.
    Weickert, Martin O.
    et al.
    Univ Hosp Coventry & Warwickshire NHS Trust, Coventry, W Midlands, England.
    Kaltsas, Gregory
    Univ Hosp Coventry & Warwickshire NHS Trust, Coventry, W Midlands, England.
    Hörsch, Dieter
    Zent Klin Bad Berka, Bad Berka, Germany.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Pavel, Marianne
    Charite, Berlin, Germany.;Friedrich Alexander Univ, Nurnberg, Germany.
    Valle, Juan W.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England.
    Caplin, Martyn E.
    Royal Free Hosp, London, England.
    Bergsland, Emily
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
    Kunz, Pamela L.
    Stanford Univ, Stanford, CA USA.
    Anthony, Lowell B.
    Univ Kentucky, Lexington, KY USA.
    Grande, Enrique
    Hosp Univ Ramon y Cajal, Madrid, Spain.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Warner, Richard R. P.
    Icahn Sch Med Mt Sinai, New York, NY USA.
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France.
    Fleming, Rosanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kittur, Ashwin
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Arnold, Karie
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Yang, Qi M.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA USA.
    Weight Change Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome2018In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 47, no 3, p. 357-358Article in journal (Other academic)
  • 41.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Couvelard, Anne
    Hospital Beaujon, Department of Pathology.
    Delle Fave, Gianfranco
    Ospedale Sant’Andrea, Department of Digestive and Liver Disease.
    Gross, David
    Hadassah University Hospital, Department of Endocrinology and Metabolism.
    Grossman, Ashley
    University of Oxford, Churchill Hospital, Oxford Centre for Diabetes, Endocrinology and Metabolism.
    Jensen, Robert T.
    National Institutes of Health, Digestive Diseases Branch.
    Pape, Ulrich-Frank
    Charité University of Berlin, Department of Internal Medicine.
    Perren, Aurel
    niversity Hospital Zurich, Department of Pathology.
    Rindi, Guido
    Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Institute of Anatomic Pathology.
    Ruszniewski, Philippe
    Beaujon Hopital, Department of Gastroenterology.
    Scoazec, Jean-Yves
    Gustave Roussy Institute, Department of Biopathology, Faculty of Medicine Paris Sud.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Wiedenmann, Bertram
    Charité University Medicine, Department of Hepatology and Gastroenterology.
    Ferone, Diego
    University of Genova, IRCCS AOU San Martino IST, DiMI, CEBR.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 201-211Article in journal (Refereed)
    Abstract [en]

    Biomarkers have been the mainstay in the diagnosis and follow-up of patients with neuroendocrine tumors (NETs) over the last few decades. In the beginning, secretory products from a variety of subtypes of NETs were regarded as biomarkers to follow during diagnosis and treatment: serotonin for small intestinal (SI) NETs, and gastrin and insulin for pancreatic NETs. However, it became evident that a large number of NETs were so-called nonfunctioning tumors without secreting substances that caused hormone-related symptoms. Therefore, it was necessary to develop so-called "general tumor markers." The most important ones so far have been chromogranin A and neuron-specific enolase (NSE). Chromogranin A is the most important general biomarker for most NETs with a sensitivity and specificity somewhere between 60 and 90%. NSE has been a relevant biomarker for patients with high-grade tumors, particularly lung and gastrointestinal tract tumors. Serotonin and the breakdown product urinary 5-hydroxyindoleacetic acid (U-5-HIAA) is still an important marker for diagnosing and follow-up of SI NETs. Recently, 5-HIAA in plasma has been analyzed by highperformance liquid chromatography and fluorometric detection and has shown good agreement with U-5-HIAA anal ysis. In the future, we will see new tests including circulating tumor cells, circulating DNA and mRNA. Recently, a NET test has been developed analyzing gene transcripts in circulating blood. Preliminary data indicate high sensitivity and specificity for NETs. However, its precise role has to be validated in prospective randomized controlled trials which are ongoing right now.

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