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Welin, Staffan
Publications (10 of 50) Show all publications
Ramage, J. K., Valle, J., Nieveen van Dijkum, E. J., Sundin, A., Pascher, A., Couvelard, A. & Kloeppel, G. (2019). Colorectal Neuroendocrine Neoplasms - areas of unmet need. Neuroendocrinology, 108(1), 45-53
Open this publication in new window or tab >>Colorectal Neuroendocrine Neoplasms - areas of unmet need
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 45-53Article in journal (Refereed) Published
Abstract [en]

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

Keywords
Carcinoid tumours, Gastroenteropancreatic neuroendocrine tumours, Neuroendocrine tumour, Somatostatin receptor
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-362622 (URN)10.1159/000493767 (DOI)000456048400006 ()30219817 (PubMedID)
Note

ENETS 2016 Munich Advisory Board, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan.

Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-02-11Bibliographically approved
Crona, J., Lamarca, A., Ghosal, S., Welin, S., Skogseid, B. & Pacak, K. (2019). Genotype-phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis. Endocrine-Related Cancer, 26(5), 539-550
Open this publication in new window or tab >>Genotype-phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis
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2019 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 26, no 5, p. 539-550Article, review/survey (Refereed) Published
Abstract [en]

Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with SDHB mutation (OR 5.68 (95% CI 1.79-18.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02-8.79)) and dopa mine (OR 6.39 (95% CI 1.62-25.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02-1.06)) and metastases (HR 6.13 (95% CI 2.86-13.13)) but neither paraganglioma nor SDHB mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to SDHB provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.

Place, publisher, year, edition, pages
BIOSCIENTIFICA LTD, 2019
Keywords
pheochromocytoma, paraganglioma, molecular genetics, driver mutations, meta-analysis
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-383282 (URN)10.1530/ERC-19-0024 (DOI)000465198700009 ()30893643 (PubMedID)
Available from: 2019-05-14 Created: 2019-05-14 Last updated: 2019-10-30Bibliographically approved
Capdevila, J., Bodei, L., Davies, P., Gorbounova, V., Jensen, R. T., Knigge, U. P., . . . Pavel, M. E. (2019). Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms. Neuroendocrinology, 108(1), 18-25
Open this publication in new window or tab >>Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 18-25Article in journal (Refereed) Published
Abstract [en]

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

Keywords
Biomarkers, Imaging, Metastasis, Neuroendocrine neoplasms, Therapy, Unmet medical needs
National Category
Endocrinology and Diabetes Psychiatry
Identifiers
urn:nbn:se:uu:diva-375573 (URN)10.1159/000493319 (DOI)000456048400003 ()30153686 (PubMedID)
Note

ENETS 2016 Munich Advisory Board Participants, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan.

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Baudin, E., Hayes, A. R., Scoazec, J.-Y., Filosso, P. L., Lim, E., Kaltsas, G., . . . Caplin, M. E. (2019). Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms. Neuroendocrinology, 108(1), 7-17
Open this publication in new window or tab >>Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 7-17Article in journal (Refereed) Published
Abstract [en]

Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.

Keywords
Bronchial carcinoid tumours, NET, Neuroendocrine neoplasms, Pulmonary carcinoids
National Category
Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-375567 (URN)10.1159/000493980 (DOI)000456048400002 ()30248673 (PubMedID)
Note

ENETS 2016 Munich Advisory Board Participants (UU authors): Jenny Falkerby; Anders Sundin; Eva Tiensuu Janson & Staffan Welin

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Toumpanakis, C., Fazio, N., Tiensuu Janson, E., Hörsch, D., Pascher, A., Reed, N., . . . Scoazec, J.-Y. (2019). Unmet Needs in Appendiceal Neuroendocrine Neoplasms. Neuroendocrinology, 108(1), 37-44
Open this publication in new window or tab >>Unmet Needs in Appendiceal Neuroendocrine Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 37-44Article in journal (Refereed) Published
Abstract [en]

Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course; thus, appendicectomy alone is considered curative. However, in some cases, a malignant potential is suspected, and therefore additional operations such as completion right hemicolectomy are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide useful data about epidemiology and prognosis, as well as practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, these guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust, and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, as well as identified risk factors that would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are adopting a critical approach of the ENETS guidelines and published series for ANEN, focusing on the above-noted "grey areas".

Keywords
Appendiceal neuroendocrine neoplasms, Appendicectomy, Appendix, Carcinoids, Right hemicolectomy
National Category
Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:uu:diva-375571 (URN)10.1159/000493894 (DOI)000456048400005 ()30235454 (PubMedID)
Note

ENETS 2016 Munich Advisory Board, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Jensen, R. T., Bodei, L., Capdevila, J., Couvelard, A., Falconi, M., Grozinsky-Glasberg, S., . . . Fazio, N. (2019). Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine neoplasms. Neuroendocrinology, 108(1), 26-36
Open this publication in new window or tab >>Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 26-36Article in journal (Refereed) Published
Abstract [en]

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

National Category
Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:uu:diva-362648 (URN)10.1159/000494258 (DOI)000456048400004 ()30282083 (PubMedID)
Note

ENETS 2016 Munich Advisory Board, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan

Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-02-11Bibliographically approved
Sorbye, H., Baudin, E., Borbath, I., Caplin, M., Chen, J., Cwikla, J. B., . . . Garcia-Carbonero, R. (2019). Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3). Neuroendocrinology, 108(1), 54-62
Open this publication in new window or tab >>Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 54-62Article in journal (Refereed) Published
Abstract [en]

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.

Keywords
Neuroendocrine carcinoma, Neuroendocrine neoplasm, Neuroendocrine tumor
National Category
Neurosciences Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-375598 (URN)10.1159/000493318 (DOI)000456048400007 ()30153658 (PubMedID)
Note

ENETS 2016 Munich Advisory Board, Uppsala University: Falkerby, Jenny; Sundin, Anders; Tiensuu Janson, Eva & Welin, Staffan.

Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-02-11Bibliographically approved
Daskalakis, K., Karakatsanis, A., Hessman, O., Stuart, H. C., Welin, S., Tiensuu Janson, E., . . . Stålberg, P. (2018). Association of a Prophylactic surgical approach to Stage IV Small Intestinal Neuroendocrine Tumors with Survival.. JAMA Oncology, 4(2), 183-189
Open this publication in new window or tab >>Association of a Prophylactic surgical approach to Stage IV Small Intestinal Neuroendocrine Tumors with Survival.
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2018 (English)In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 2, p. 183-189Article in journal (Refereed) Published
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.

 

Keywords
Small Intestinal NETs, prophylactic loco-regional surgery, stage IV
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-330702 (URN)10.1001/jamaoncol.2017.3326 (DOI)000424778600010 ()29049611 (PubMedID)
Funder
Göran Gustafsson Foundation for Research in Natural Sciences and MedicineSwedish Cancer Society
Available from: 2017-10-21 Created: 2017-10-03 Last updated: 2018-04-16Bibliographically approved
Weickert, M. O., Kaltsas, G., Hörsch, D., Lapuerta, P., Pavel, M., Valle, J. W., . . . Kulke, M. H. (2018). Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clinical Therapeutics, 40(6), 952-962
Open this publication in new window or tab >>Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
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2018 (English)In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 40, no 6, p. 952-962Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ELSEVIER, 2018
Keywords
carcinoid syndrome, carcinoid syndrome diarrhea, malnutrition, neuroendocrine tumor, telotristat ethyl, weight
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-360481 (URN)10.1016/j.clinthera.2018.04.006 (DOI)000437389200017 ()29724499 (PubMedID)
Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2018-09-17Bibliographically approved
Ali, A. A., Grönberg, M., Hjortland, G. O., Grønbæk, H., Ladekarl, M., Langer, S. W., . . . Tiensuu Janson, E. (2018). Intravenous versus Oral Etoposide: Efficacy and Correlation to Clinical Outcome in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3). Paper presented at 15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN. Neuroendocrinology, 106(Supplement: 1), 184-184
Open this publication in new window or tab >>Intravenous versus Oral Etoposide: Efficacy and Correlation to Clinical Outcome in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)
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2018 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 184-184Article in journal, Meeting abstract (Other academic) Published
Keywords
chemotherapy, neuroendocrine neoplasms, intravenous, oral, survival
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-355844 (URN)10.1159/000487699 (DOI)000427285300182 ()
Conference
15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN
Note

Meeting Abstract: H01

Available from: 2018-07-13 Created: 2018-07-13 Last updated: 2018-07-13Bibliographically approved
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