liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 67) Show all publications
Welander, J., Gustavsson, I., Ekman, C., Brauckhoff, M., Brunaud, L., Söderkvist, P. & Gimm, O. (2018). Activating FGFR1 mutations in sporadic pheochromocytoma. World Journal of Surgery, 42(2), 482-489
Open this publication in new window or tab >>Activating FGFR1 mutations in sporadic pheochromocytoma
Show others...
2018 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 482-489Article in journal (Other academic) Published
Abstract [en]

Pheochromocytomas are neuroendocrine tumors of the adrenal glands that cause hypertension. More than a third of the cases are associated with hereditary mutations in a growing list of susceptibility genes, some of which are also somatically altered in sporadic pheochromocytomas. However, for the majority of sporadic pheochromocytomas, a genetic explanation is still lacking. Here we investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples, and discovered on average 33 non-silent somatic mutations per tumor. One of the recurrently mutated genes was FGFR1, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pilocytic astrocytoma and childhood glioblastoma. Including a subsequent analysis of a larger cohort, activating FGFR1  mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with NF1- RET- and HRAS-mutated pheochromocytomas, indicating activation of the MAPK and PI3K-AKT signal transduction pathways. The results advance our biological understanding of pheochromocytoma and suggest that somatic FGFR1 activation is an important event in a subset of these tumors.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114805 (URN)10.1007/s00268-017-4320-0 (DOI)000419886700025 ()29159601 (PubMedID)
Note

Funding agencies: Linkoping University; Swedish Cancer Society; FORSS; LiU Cancer

Available from: 2015-03-04 Created: 2015-03-04 Last updated: 2018-04-25Bibliographically approved
Toledo, R. A., Burnichon, N., Cascon, A., Benn, D. E., Bayley, J.-P., Welander, J., . . . Dahia, P. L. M. (2017). Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas. Nature Reviews Endocrinology, 13(4), 233-247
Open this publication in new window or tab >>Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas
Show others...
2017 (English)In: Nature Reviews Endocrinology, ISSN 1759-5029, E-ISSN 1759-5037, Vol. 13, no 4, p. 233-247Article in journal (Refereed) Published
Abstract [en]

Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-136039 (URN)10.1038/nrendo.2016.185 (DOI)000396002800006 ()27857127 (PubMedID)
Note

Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

Available from: 2017-03-27 Created: 2017-03-27 Last updated: 2018-05-02
Haj-Hosseini, N., Gimm, O., Höög, A. & Johansson, K. (2017). Optiska metoder för identifiering av bisköldkörtel och sköldkörtel. In: : . Paper presented at Kirurgveckan, Jönköping, Sweden, Augusti 21-25, 2017. Jönköping, Sweden
Open this publication in new window or tab >>Optiska metoder för identifiering av bisköldkörtel och sköldkörtel
2017 (Swedish)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [sv]

Identifiering av bisköldkörtlar är viktigt vid sköldkörtel- och bisköldkörtelkirurgi och kan vara svårt då de liknar omgivande vävnad såsom fett och lymfkörtlar. Peroperativ detektering av dessa vävnader kan förbättra möjligheten att bota patienter med hyperparathyroidism och minska risken för bisköldkörtelskador vid thyroideakirurgi. Optiska metoder är potentiella tekniker för att möjliggöra detta. Optiska tekniker utvärderades på vävnadsprover från patienter vid bisköldkörtel- och sköldkörteloperation. Teknikerna bestod av nära infraröd fluorescens (NIR) spektroskopi och optisk koherenstomografi (OCT) som ger en bild av vävnadens mikrostruktur liknande till ultraljud med högre upplösning (10 μm).

Place, publisher, year, edition, pages
Jönköping, Sweden: , 2017
Keywords
sköldkörtel, bisköldkörtel, kirurgi, optiska metoder, optisk koherenstomografi, fluorescens
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-140898 (URN)
Conference
Kirurgveckan, Jönköping, Sweden, Augusti 21-25, 2017
Available from: 2017-09-14 Created: 2017-09-14 Last updated: 2018-04-25Bibliographically approved
Aljabery, F., Shabo, I., Olsson, H., Gimm, O. & Jahnson, S. (2017). Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.. BJU International, 120(3), 329-336
Open this publication in new window or tab >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
Show others...
2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2017
Keywords
#BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
Note

Funding agencies: County Council of Ostergotland, Linkoping, Sweden

Available from: 2017-05-01 Created: 2017-05-01 Last updated: 2018-05-03
Paulsson, J. O., Svahn, F., Welander, J., Brunaud, L., Söderkvist, P., Gimm, O., . . . Juhlin, C. C. (2016). Editorial Material: Absence of the BRAF V600E mutation in pheochromocytoma in JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol 39, issue 6, pp 715-716. Journal of Endocrinological Investigation, 39(6), 715-716
Open this publication in new window or tab >>Editorial Material: Absence of the BRAF V600E mutation in pheochromocytoma in JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol 39, issue 6, pp 715-716
Show others...
2016 (English)In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 39, no 6, p. 715-716Article in journal, Editorial material (Other academic) Published
Abstract [en]

Purpose Pheochromocytomas (PCCs) are rare endocrine tumors originating from the adrenal medulla. These tumors display a highly heterogeneous mutation profile, and a substantial part of the causative genetic events remains to be explained. Recent studies have reported presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. This study sought to further investigate the occurrence of the BRAF V600E mutation in these tumors. Methods A cohort of 110 PCCs was screened for the BRAF V600E mutation using direct Sanger sequencing. Results All cases investigated displayed wild-type sequences at nucleotide 1799 in the BRAF gene. Conclusions Taken together with all previously screened tumors up to date, only 1 BRAF V600E mutation has been found among 361 PCCs. These findings imply that the BRAF V600E mutation is a rare event in pheochromocytoma.

Place, publisher, year, edition, pages
SPRINGER, 2016
Keywords
Adrenal; Pheochromocytoma; Sequencing; BRAF; Mutation
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-129146 (URN)10.1007/s40618-015-0420-6 (DOI)000375920000013 ()26710756 (PubMedID)
Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2018-04-25
Stenman, A., Welander, J., Gustavsson, I., Brunaud, L., Backdahl, M., Söderkvist, P., . . . Larsson, C. (2016). HRAS mutation prevalence and associated expression patterns in pheochromocytoma. Genes, Chromosomes and Cancer, 55(5), 452-459
Open this publication in new window or tab >>HRAS mutation prevalence and associated expression patterns in pheochromocytoma
Show others...
2016 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 55, no 5, p. 452-459Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo-hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been verified in sporadic PPGLs. In order to further establish the HRAS mutation frequency and to characterize the associated expression profiles of HRAS mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the HRAS gene was screened, and compared with microarray-based gene expression profiles for 93 of the cases. The activating HRAS mutations G13R, Q61R, and Q61K were found in 10/142 PCC (7.0%) and a Q61L mutation was revealed in 1/14 PGL (7.1%). All HRAS mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 HRAS wild-type PPGL. Somatic HRAS mutations were not revealed in cases with known PPGL susceptibility gene mutations and all HRAS mutated cases were benign. The HRAS mutation prevalence of all PPGL published up to date is 5.2% (49/950), and 8.8% (48/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of HRAS mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. HRAS mutated PPGL cluster together with NF1- and RET-mutated tumors associated with activation of kinase-signaling pathways.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127407 (URN)10.1002/gcc.22347 (DOI)000372913800005 ()26773571 (PubMedID)
Note

Funding Agencies|Swedish Cancer Foundation; StratCan; Swedish Research Council; Cancer Research Foundations of Radiumhemmet; Karolinska Institutet; Stockholm County Council

Available from: 2016-05-02 Created: 2016-04-26 Last updated: 2018-04-25
Haj-Hosseini, N., Petersson, P., Gimm, O. & Shabo, I. (2016). Optical Coherence Tomography for Pathological Analysis of Thyroid. In: : . Paper presented at SPIE Photonics West, 16 - 18-February 2016 San Francisco, California, United States. San Francisco
Open this publication in new window or tab >>Optical Coherence Tomography for Pathological Analysis of Thyroid
2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
San Francisco: , 2016
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-126690 (URN)
Conference
SPIE Photonics West, 16 - 18-February 2016 San Francisco, California, United States
Funder
Medical Research Council of Southeast Sweden (FORSS)Linköpings universitet
Available from: 2016-04-01 Created: 2016-04-01 Last updated: 2018-04-25
Carlander, J., Wagner, P., Gimm, O., Nordenström, E., Jansson, S., Bergkvist, L. & Johansson, K. (2016). Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study. World Journal of Surgery, 40(1), 117-123
Open this publication in new window or tab >>Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study
Show others...
2016 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 1, p. 117-123Article in journal (Refereed) Published
Abstract [en]

Background

Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time.

Materials and methods

The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88 % of the thyroid procedures performed during 2008–2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used.

Results

The thyroid procedures performed included C-A-T (16.6 %), bipolar electrosurgery (ES: 56.5 %), electronic vessel sealing (EVS: 12.2 %), and ultrasonic dissection (UD: 14.5 %). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T.

Conclusion

In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-122146 (URN)10.1007/s00268-015-3270-7 (DOI)000367465500015 ()26470699 (PubMedID)
Note

Funding agencies: FORSS (Forskningsradet i Sydostra Sverige)

Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2018-04-25Bibliographically approved
Stenman, A., Svahn, F., Welander, J., Gustavson, B., Söderkvist, P., Gimm, O. & Juhlin, C. C. (2015). Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma.. Endocrine pathology, 26(1), 9-14
Open this publication in new window or tab >>Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma.
Show others...
2015 (English)In: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 26, no 1, p. 9-14Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCCs) are tumors originating from the adrenal medulla displaying a diverse genetic background. While most PCCs are sporadic, about 40 % of the tumors have been associated with constitutional mutations in one of at least 14 known susceptibility genes. As 25 % of sporadic PCCs harbor somatic neurofibromin 1 gene (NF1) mutations, NF1 has been established as the most recurrently mutated gene in PCCs. To be able to pinpoint NF1-related pheochromocytoma (PCC) disease in clinical practice could facilitate the detection of familial cases, but the large size of the NF1 gene makes standard DNA sequencing methods cumbersome. The aim of this study was to examine whether mutations in the NF1 gene could be predicted by immunohistochemistry as a method to identify cases for further genetic characterization. Sixty-seven PCCs obtained from 67 unselected patients for which the somatic and constitutional mutational status of NF1 was known (49 NF1 wild type, 18 NF1 mutated) were investigated for NF1 protein immunoreactivity, and the results were correlated to clinical and genetic data. NF1 immunoreactivity was absent in the majority of the PCCs (44/67; 66 %), including 13 out of 18 cases (72 %) with a somatic or constitutional NF1 mutation. However, only a minority of the NF1 wild-type PCCs (18/49; 37 %) displayed retained NF1 immunoreactivity, thereby diminishing the specificity of the method. We conclude that NF1 immunohistochemistry alone is not a sufficient method to distinguish between NF1-mutated and non-mutated PCCs. In the clinical context, genetic screening therefore remains the most reliable tool to detect NF1-mutated PCCs.

Place, publisher, year, edition, pages
Springer, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-115262 (URN)10.1007/s12022-014-9348-1 (DOI)000350057500002 ()25403449 (PubMedID)
Available from: 2015-03-11 Created: 2015-03-11 Last updated: 2018-04-25Bibliographically approved
Haj-Hosseini, N., Stepp, H., Markwardt, N., Gimm, O. & Shabo, I. (2015). Optical biopsy during thyroid and parathyroid surgery. In: : . Paper presented at European Conferences on Biomedical Optics, Munich, Germany, 21-25 June. Munich: SPIE - International Society for Optical Engineering
Open this publication in new window or tab >>Optical biopsy during thyroid and parathyroid surgery
Show others...
2015 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
Munich: SPIE - International Society for Optical Engineering, 2015
Keywords
optical coherence tomography, autofluorescene, thyroid, parathyroid
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-118520 (URN)
Conference
European Conferences on Biomedical Optics, Munich, Germany, 21-25 June
Funder
Medical Research Council of Southeast Sweden (FORSS)
Available from: 2015-05-29 Created: 2015-05-29 Last updated: 2018-04-25Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0054-664x

Search in DiVA

Show all publications