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  • 101.
    Skogseid, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Experience with multiple endocrine neoplasia type 1 screening1995In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 238, no 3, p. 255-261Article in journal (Refereed)
    Abstract [en]

    Screening for multiple endocrine neoplasia type 1 (MEN1) may be conducted for a variety of reasons. The principal aims may be more or less scientific, such as early identification of the trait. Other reasons for screening comprise attempts to avoid endocrine morbidity and possibly forthcoming problems from malignant transformation, as well as attempts to identify and treat gene carriers with a clinically overt disease. Several reports have substantiated the diagnostic yield from screening efforts among MEN1 kindreds. Such increases in detection of the disease ideally should be accompanied by enhanced rates of survival in order to fully justify an unlimited search for the trait. However, studies are lacking a clearly verifying reduction of mortality from the detection of presymptomatic MEN1 individuals. While waiting for the results of survival studies in progress, the generally prevailing opinion favours widespread screening because of the evidently decreased morbidity resulting from early diagnosis of the MEN1 trait, which apparently persists even during decades of follow-up. This paper presents the clinical features of the disease and experience derived from a prospective screening programme for MEN1 detection.

  • 102.
    Skogseid, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Genetics of multiple endocrine neoplasia type 11995In: Endocrine tumors of the pancreas: recent advances in research and management / [ed] M Mignon, R T Jensen, Basel: S. Karger, 1995Chapter in book (Other academic)
  • 103.
    Skogseid, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgery for asymptomatic pancreatic lesion in multiple endocrine neoplasia type I1996In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 20, no 7, p. 872-877Article in journal (Refereed)
    Abstract [en]

    Patients with multiple endocrine neoplasia (MEN) type I underwent pancreatic surgery at presymptomatic (n = 8, mean age 33 years) or symptomatic (n = 12, mean age 51 years) stages of pancreatic endocrine involvement with the principal aim to evaluate postoperative morbidity, survival, and malignant potential of the pancreatic lesion. Radiologic signs of malignancy were not identified in any patient prior to exploration. All patients displayed multiple tumors with generally complex immunoreactivity. Normal postoperative pancreatic tumor markers were recorded in five of the asymptomatic patients, which became abnormal in three of them at a mean of 3 years after surgery. All patients remained without symptoms for a mean of 6 years after operation. In four symptomatic individuals (33%) metastases were identified at exploration, and two died with tumor; 83% of symptomatic patients displayed persistent or recurrent endocrine morbidity from the pancreatic lesion. Recognizing lead time bias, this limited and uncontrolled patient comparison suggests that exploration at the symptomatic stage of pancreatic involvement in MEN-I patients is unsatisfactory. Rather than to obtain biochemical cure, surgery in asymptomatic patients might be regarded as a means of cancer prevention. The malignancy of the pancreatic lesion may be preceded by several decades of biochemical abnormality. Extensive screening for this lesion allows diagnosis during adolescence and the timely application of primary exploration. Active management of individuals with repeated biochemical analyses followed by selective reintervention could enable satisfactorily maintained pancreatic functions and substantial duration of cancer prevention.

  • 104.
    Skogseid, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Westlin, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eklöf, Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Elvin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration: can it be predicted by preoperative tumor localization?1998In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 22, no 7, p. 673-677; discussion 667-668Article in journal (Refereed)
    Abstract [en]

    Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions </= 1 cm in diameter on palpation, intraoperative ultrasonography, and microscopy. It occurred in 37% and 50% of the patients with and without radiologic tumor localization, respectively. The number of positive tumor markers was similar for patients with limited and major disease (2.3 vs. 2.7), whereas four or more such markers were found in all those with malignancies. The mean marker level was higher in patients with radiologically demonstrable tumors and lower in those with limited disease, but with a substantial overlap. OctreoScan testing was negative in all cases with limited disease and was the single most sensitive method (75%) in the others. Limited pancreatic disease could not be identified preoperatively, and the present means of biochemical pancreatic tumor identification invariably involved the presence of at least one lesion >/= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.

  • 105.
    Staaf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Ljungström, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hög tid att söka till nya MD/PhD-programmet vid Uppsala universitet: Tidig bro mellan preklinisk forskning och klinik2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 17-18, p. 898-898Article in journal (Refereed)
  • 106.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lundqvist, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Islet amyloid polypeptide (IAPP) in patients with neuroendocrine tumours1995In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 55, no 2, p. 119-131Article in journal (Refereed)
    Abstract [en]

    Although IAPP was first discovered and isolated from amyloid deposits in an endocrine pancreatic tumour (EPT), surprisingly few reports have investigated the potential use of IAPP as a marker for neuroendocrine tumour growth. In this study we present results from plasma measurements of IAPP in 102 patients with neuroendocrine tumours. Four of 35 patients (11%) with midgut carcinoid tumours, but none of the patients (4 and 5, respectively) with lung carcinoids or with rectal carcinoids displayed elevated plasma levels of IAPP. Five of 31 patients (16%) with sporadic EPT and 3 of 27 patients (11%) with EPT and multiple endocrine neoplasia type 1 syndrome disclosed elevated IAPP levels. Within the different syndromes, 1/11 individuals with insulinoma, 2/16 with gastrinoma, 0/2 with glucagonoma, 0/3 with VIPoma and 5/26 with non-functioning tumours showed elevated plasma levels of IAPP. In two patients, the plasma IAPP levels were extremely elevated. These patients also exhibited altered glucose homeostasis. In response to a standardised mixed meal test, IAPP increased in parallel to the insulin, pancreatic polypeptide, gastrin and glucose responses. In MEN1 patients with hypercalcaemia due to increased secretion of parathyroid hormone, the plasma levels of IAPP were significantly higher before than after surgical removal of the parathyroid adenomas. However in normocalcaemic patients, no correlation between the blood calcium and plasma IAPP levels was found. Immunocytochemical staining of tumour tissue showed that 9/13 (69%) of insulin producing tumours, 4/14 (29%) of non-functioning tumours and 1/9 (11%) of gastrin producing tumours were IAPP immunoreactive. Amyloid deposits were always IAPP immunoreactive. In conclusion, increased circulating levels of IAPP occurred in 12% of 102 patients with neuroendocrine tumours. In 2 patients with extremely elevated plasma levels of IAPP, effects on glucose homeostasis were recorded. Thus, IAPP may be useful as an additional marker for neuroendocrine tumour growth in selected cases.

  • 107.
    Stålberg, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Razmara, Masoud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Taslica, Diana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Ståhlberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    An Integrative Genomic Analysis of Formalin Fixed Paraffin-Embedded Archived Serous Ovarian Carcinoma Comparing Long-term and Short-term Survivors2016In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 26, no 6, p. 1027-1032Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study aimed to perform an integrative genetic analysis of patients with matched serous ovarian cancer having long-term or short-term survival using formalin fixed paraffin-embedded (FFPE) tissue samples.

    METHODS:

    All patients with serous ovarian carcinoma who underwent surgery between 1998 and 2007 at the Department of Gynaecology, Uppsala University Hospital, Sweden were considered. From this cohort, we selected biomaterial from 2 groups of patients with long-term and short-term survival matched for age, stage, histologic grade, and outcome of surgery. Genomic DNA from FFPE sample was analyzed with SNP array and targeted next-generation sequencing of 26 genes.

    RESULTS:

    Forty-three samples (primary tumors and metastases) from 23 patients were selected for genomic profiling, the survival in the subgroups were 134 and 36 months, respectively. We observed a tendency toward increased genomic instability in those with long-term survival with higher proportion of somatic copy number alterations (P = 0.083) and higher average ploidy (P = 0.037). TP53 mutations were found in 50% of the patients. Frequency of TP53 mutations did not differ between the survival groups (P = 0.629).

    CONCLUSIONS:

    We validated both previous genomic findings in ovarian cancer and the proposed association between increased genomic instability and better survival. These results exemplify that analysis of genomic biomarkers is feasible on archived FFPE tissue.

  • 108.
    Stålberg, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lopez-Egido, J R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wang, S
    Gobl, A
    Oberg, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Skogseid, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Differentially expressed cDNAs in PLCbeta3-induced tumor suppression in a human endocrine pancreatic tumor cell line: activation of the human mismatch repair protein 3 gene.2001In: Biochem Biophys Res Commun, ISSN 0006-291X, Vol. 281, no 1, p. 227-31Article in journal (Refereed)
  • 109.
    Stålberg, Peter
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Granberg, Dan
    Department of Medical Sciences.
    Carling, Tobias
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Wilander, Erik
    Department of Genetics and Pathology.
    Eriksson, Barbro
    Department of Medical Sciences.
    Gobl, Anders
    Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Rastad, Jonas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Modlin, Irvin M
    Oberg, Kjell
    Department of Medical Sciences.
    Skogseid, Britt
    Department of Medical Sciences.
    In Situ RNA-RNA Hybridization of Phospholipase C β3 Shows Lack of Expression in Neuroendocrine Tumours2003In: Anticancer Research, Vol. 23, no 3B, p. 2227-2232Article in journal (Refereed)
  • 110.
    Stålberg, Peter
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Endokrin tumörbiologi.
    Grimfjärd, Per
    Department of Medical Sciences.
    Santesson, Mårten
    Department of Medical Sciences.
    Zhou, Yinghua
    Department of Medical Sciences. Onkologisk endokrinologi.
    Lindberg, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gobl, Anders
    Department of Medical Sciences.
    Öberg, Kjell
    Department of Medical Sciences. Onkologisk endokrinologi.
    Westin, Gunnar
    Rastad, Jonas
    Wang, Shu
    Department of Medical Sciences. Endokrin tumörbiologi.
    Skogseid, Britt
    Department of Medical Sciences. Endokrin tumörbiologi.
    Transfection of the multiple endocrine neoplastia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of junD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen and QM/Jif-12004In: The journal of clinical endocrinology & metabolism, Vol. 5, p. 2326-2337Article in journal (Refereed)
  • 111.
    Stålberg, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Santesson, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekeblad, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Recognizing genes differentially regulated in vitro by the multiple endocrine neoplasia type 1 (MEN1) gene, using RNA interference and oligonucleotide microarrays2006In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 140, no 6, p. 921-931Article in journal (Refereed)
    Abstract [en]

    Background:

    Data on downstream effects of MEN1 gene inactivation is scarce. In an effort to identify genes regulated by MEN1, we designed a silencing experiment in a human endocrine pancreatic tumor cell line (BON1).

    Methods:

    By using RNA interference, MEN1 mRNA expression was knocked-down by >85%. Gene expression was assessed by oligonucleotide microarrays and compared to expression in nonsilenced controls. We also investigated if genes were differentially expressed in 6 malignant endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation compared to 2 without MEN1 gene alterations.

    Results:

    Using a cut-off of ≥2 times, 66 genes were found to be upregulated, and 22 were downregulated in the MEN1-silenced clones. We corroborated the microarray findings by performing quantitative-PCR on the RNA from the silencing experiments for 7 of the 88 differentially regulated genes. Genes involved in endocrine cell fate determination, as well as genes known to be involved in NFkappaB, Notch, and Wnt signaling pathways, were among genes verified as differentially regulated in vitro.

    Conclusions:

    The demonstration of pathways affected by silencing of MEN1 in vitro provides novel insight into neoplastic processes of potential importance in vivo, which warrants further study.

  • 112.
    Stålberg, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wang, Shu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Weber, Günther
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gobl, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Suppression of the neoplastic phenotype by transfection of phospholipase C3 to neuroendocrine tumor cells1999In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 450, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    The expression of phospholipase C beta 3 (PLCB3) is low or absent in several neuroendocrine neoplasias. To investigate the role of PLCB3 in the neuroendocrine tumorigenesis, we transfected a PLCB3 construct to three neuroendocrine tumor cell lines with a low PLCB3 expression. The growth rate and tumorigenicity were assessed in vitro by [3H]thymidine incorporation and cell counting, in vivo, by xenografting to nude mice. In vitro, PLCB3 expressing clones showed a significant growth inhibition. The tumor weight was reduced for one of the two xenografted PLCB3-transfected cell lines and in both, a reduced number of proliferating (Ki-67 positive) cells was observed. This study implies an essential role for PLCB3 in the neuroendocrine tumorigenesis.

  • 113. Tacon, Lyndal J.
    et al.
    Soon, Patsy S.
    Gill, Anthony J.
    Chou, Angela S.
    Clarkson, Adele
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Stålberg, Peter L. H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Robinson, Bruce G.
    Sidhu, Stanley B.
    Clifton-Bligh, Roderick J.
    The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors2009In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 11, p. 4591-4599Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies.

    OBJECTIVE:

    Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score.

    DESIGN:

    Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed.

    RESULTS:

    Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001).

    CONCLUSIONS:

    The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.

  • 114. Teh, Bin T
    et al.
    Zedenius, J
    Kytola, S
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Trotter, J
    Choplin, H
    Twigg, S
    Farnebo, F
    Giraud, S
    Cameron, D
    Robinson, B
    Calender, A
    Larsson, C
    Salmela, P
    Thymic carcinoids in multiple endocrine neoplasia type 11998In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 228, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1.

    SUMMARY BACKGROUND DATA:

    Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown.

    METHODS:

    Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities.

    RESULTS:

    Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region.

    CONCLUSIONS:

    MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved.

  • 115. Tham, Emma
    et al.
    Grandell, Ulla
    Lindgren, Eva
    Toss, Göran
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordenskjöld, Magnus
    Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 9, p. 3389-3395Article in journal (Refereed)
    Abstract [en]

    Context: Multiple endocrine neoplasia type 1 (MEN1) is a tumor syndrome of the parathyroid, endocrine pancreas, and anterior pituitary caused by mutations in the MEN1 gene on 11q13. Objective: The goal of this study was to determine the MEN1 mutation spectrum and detection rate among Swedish patients and identify which patient categories should be tested for MEN1 mutations. Design/Setting/Patients: DNA sequences and referral forms from patients referred to the Department of Clinical Genetics at Karolinska University Hospital, Sweden, for clinical MEN1 mutation screening were analyzed. The mutation status of 371 patients (including 200 probands) was ascertained, and the multiplex ligation-dependent probe amplification (MLPA) assay was evaluated for the detection of large deletions. Main Outcome Measure: The main outcome measure was MEN1 genotypes. Results: Forty-eight of 200 index cases (24%) shared 40 different mutations (18 novel). A total of 69% of all mutations resulted in a truncated protein. Two large deletions were detected by MLPA. A total of 94% of all MEN1 families had a mutation in the coding region of the MEN1 gene. A total of 6% of sporadic cases had MEN1 mutations. There was no correlation between severe disease and mutation type or location. Conclusions: A total of 4% of all mutations were large deletions, and MLPA is now included in our standard MEN1 mutation screening. Individuals with at least one typical endocrine tumour and at least one of the following: 1) a first-degree relative with a major endocrine tumor; 2) an age of onset less than 30 yr; and/or 3) multiple pancreatic tumors/parathyroid hyperplasia were most likely to harbor a mutation; thus these patients should be screened for MEN1 mutations.

  • 116.
    Tiensuu Janson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öhrvall, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Westlin, Jan-Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Treatment with high dose [(111)In-DTPA-D-PHE1]-octreotide in patients with neuroendocrine tumors: evaluation of therapeutic and toxic effects1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 373-377Article in journal (Refereed)
    Abstract [en]

    Carcinoid tumors and endocrine pancreatic tumors often express somatostatin receptors (sst). Tumor spread may be visualized by sst scintigraphy using [(111)In-DTPA-D-Phe1]-octreotide. In this study, tumor targeting therapy with [(111)In-DTPA-D-Phe1]-octreotide at high doses (6 GBq every third week) was used to treat patients with sst-expressing tumors. Five patients entered the protocol and three were evaluable for response, while all could be evaluated for toxicity. Two patient responded with a significant reduction in tumor markers (> 50%). The third patient showed increasing levels of tumor markers. Side effects were expressed as depression of bone-marrow function. In one patient a grade 4 reduction in platelet count was observed requiring several thrombocyte transfusions. In another two patients platelet counts decreased significantly. We conclude that treatment with [(111)In-DTPA-D-Phe1]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects.

  • 117.
    Wang, S
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lukinius, A
    Department of Genetics and Pathology.
    Zhou, Y
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Stålberg, P
    Department of Surgical Sciences.
    Gobl, A
    Oberg, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Subcellular distribution of phospholipase C isoforms in rodent pancreas and gastric mucosa.2000In: Endocrinology, ISSN 0013-7227, Vol. 141, no 7, p. 2589-93Article in journal (Refereed)
  • 118.
    Wang, She
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gebre-Medhin, S
    Betsholtz, C
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Zhou, Yinghua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, C
    Weber, G
    Feinstein, Ricardo
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gobl, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Targeted disruption of the mouse PLC b3 gene results in defective preimplantation and tumor predisposition1998In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 441, no 2, p. 261-265Article in journal (Refereed)
    Abstract [en]

    In order to investigate the biological function of phosphatidylinositol-specific phospholipase C (PLC) we generated mutant mice by gene targeting. Homozygous inactivation of PLCβ3 is lethal at embryonic day 2.5. These mutants show poor embryonic organization as well as reduced numbers of cells. Identical phenotypes were recorded in homozygous mutants generated from two independently targeted embryonic stem cell clones. Heterozygous mutant mice, however, are viable and fertile for at least two generations. We also showed that mouse PLCβ3 is expressed in unfertilized eggs, 3-cell and egg cylinder stages of embryos. In conclusion, these results indicate that PLCβ3 expression is essential for early mouse embryonic development.

  • 119.
    Wang, Shu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gebre-Medhin, Samuel
    Betsholtz, Christer
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Zhou, Yinghua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, Catharina
    Weber, Gunther
    Feinstein, Ricardo
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gobl, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Targeted disruption of the mouse phospholipase C β3 gene results in early embryonic lethality1998In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 441, no 2, p. 261-265Article in journal (Other academic)
    Abstract [en]

    In order to investigate the biological function of phosphatidylinositol-specific phospholipase C (PLC) we generated mutant mice by gene targeting. Homozygous inactivation of PLCbeta3 is lethal at embryonic day 2.5. These mutants show poor embryonic organization as well as reduced numbers of cells. Identical phenotypes were recorded in homozygous mutants generated from two independently targeted embryonic stem cell clones. Heterozygous mutant mice, however, are viable and fertile for at least two generations. We also showed that mouse PLCbeta3 is expressed in unfertilized eggs, 3-cell and egg cylinder stages of embryos. In conclusion, these results indicate that PLCbeta3 expression is essential for early mouse embryonic development.

  • 120.
    Wang, Shu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Zhou, Yinghua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Gobl, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Subcellular distribution of phospholipase C isoforms in rodent pancreas and gastric mucosa2000In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 141, no 7, p. 2589-2593Article in journal (Refereed)
    Abstract [en]

    Phosphoinositide-specific phospholipase C (PLC) has been implicated as a participant in cell proliferation as well as enzyme and hormone secretion. Defining the subcellular distribution of PLC isoforms would possibly contribute to further understanding of their function. We investigated the intracellular distribution of four PLCs (β1, β2, β3, and γ1) in mouse pancreatic cells as well as mouse and rat gastric mucosa cells by ultrastructural immunocytochemistry. In pancreatic acinar cells, PLCβ1 and PLCγ1 were demonstrated in the zymogen granules while PLCβ2 was present in the granulae as well as the endoplasmic reticulum (ER), and PLCβ3 was prominent in the ER. In the endocrine pancreas, PLCβ2 immunolabeling was expressed in the secretory granulae of α, β, δ, and pancreatic polypeptide cells. PLCβ3 showed a slight labeling in the nucleus and ER of all four pancreatic endocrine cell types while PLCγ1 was prominent in α cell granulae. In the gastric mucosa cells, PLCβ2 was highly expressed in the heterochromatin areas and in the ER of parietal, chief, mucous, and enterochromaffin-like cells. PLCβ3 were expressed in a manner similar to PLCβ2 in those cells; however, no immunoreaction was seen in the ER of parietal cell. PLCγ1 was demonstrated in the chief cell granulae. One possible, although yet speculative, interpretation of our results is that the studied PLC isoforms may be involved in processing in pancreatic secretory granulae and that nuclear PLCβ2 and PLCβ3 signaling pathways may be operative in the cells of the gastric mucosa.

  • 121.
    Wang, Shu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Zhou, Yinghua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Gobl, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Molecular cloning and characterization of a cDNA encoding mouse phospholipase C-β31998In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1393, no 1, p. 173-178Article in journal (Other academic)
    Abstract [en]

    A cDNA encoding mouse PLC-beta3 (mPLC-beta3) was identified by screening a mouse kidney cDNA library and using the rapid amplification of cDNA ends (RACE) method. The predicted open reading frame was 3705 bp in length. The deduced 1235 amino acid (aa) sequence shares 95.3% and 92% homology with the sequences of rat and human PLC-beta3, respectively. The corresponding mRNA is highly expressed in kidney, skeletal muscle, liver, lung, heart and brain. In spleen, mPLC-beta3 mRNA was not detectable, which is in contrast to humans where there is a distinct expression. Using ultrastructural immunocytochemistry, mPLC-beta3 expression was detected in the heterochromatin of the nucleus in mouse brain neurons. The observation of PLC-beta3 nuclear localization suggests that PLC-beta3 may have intranuclear functions.

  • 122. Weber, G
    et al.
    Friedman, E
    Grimmond, S
    Hayward, N K
    Phelan, C
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gobl, Anders
    Zedenius, J
    Sandelin, K
    Teh, B T
    Carson, E
    White, I
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Shepherd, J
    Nordenskjöld, M
    Larsson, C
    The phospholipase C b 3 gene located in the MEN 1 region shows loss of expression in endocrine tumors1994In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 3, no 10, p. 1775-1781Article in journal (Refereed)
    Abstract [en]

    Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour suppressor gene in this region. Identification of meiotic cross-overs in MEN1 families has placed the MEN1 locus centromeric of D11S807. An extended deletion mapping was performed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using newly isolated cDNA clones, we estimated the distance between the flanking markers D11S807 and D11S427 to be less than 900 kb. One of these cDNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no transcript was detected. Sequence characterization showed that this gene encodes for the phospholipase C beta 3, a key enzyme in signal transduction.

  • 123.
    Welin, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Eva T.
    Granberg, Dan
    Kindmark, Henrik
    Skogseid, Britt
    Öberg, Kjell
    Eriksson, Barbro
    Survival and Clinical Characteristics in 284 Patients with Malignant Midgut Carcinoid TumorsManuscript (Other academic)
  • 124.
    Welin, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lavenius, Erik
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 151, no 1, p. 107-112Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    High-dose somatostatin analogue treatment has shown an antiproliferative effect in one study including patients with neuroendocrine tumours. To explore this therapeutic strategy further, we have studied the effect of a high-dose formula of octreotide, octreotide pamoate, in midgut carcinoid patients.

    DESIGN AND METHODS:

    Twelve patients with advanced midgut carcinoid tumours with a median duration of disease of more than 5 years were included. All were in a progressive state despite several previous treatment modalities. Octreotide pamoate (160 mg) was given as an intramuscular injection every 2 weeks for 2 months and then monthly. Radiological and biochemical responses were monitored.

    RESULTS:

    Tumour size and biochemical markers were stabilised for a median of 12 months in 75% of the patients. Ten patients had symptomatic improvement of flush and diarrhoea.

    CONCLUSION:

    In this group of patients with advanced midgut carcinoid tumours and progressive disease, octreotide pamoate managed to improve symptoms, and stabilise hormone production and tumour growth in 75% of the patients. We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours.

  • 125.
    Welin, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Elevated Plasma Chromogranin A is the First Indication of Recurrence in Radically Operated Midgut Carcinoid Tumours2009In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 89, no 3, p. 302-307Article in journal (Refereed)
    Abstract [en]

    Background:

    Patients with malignant midgut carcinoids are occasionally diagnosed with limited tumor spread, and surgery with radical intention is performed. Despite curative intent, recurrences occur frequently, motivating long-term biochemical and radiological follow-up. This study aimed to compare the usefulness of various methods in detecting such recurrences.

    Methods:

    This retrospective study included 56 patients with radically operated midgut carcinoids referred to our University Hospital for evaluation and follow-up between 1985 and 2004. Patients were monitored 1-3 times per year using plasma-chromogranin A (P-CgA), urinary 5-hydroxyindoleacetic acid (U-5HIAA) concentrations as well as radiological examinations, including ultrasonography, computerized tomography or magnetic resonance investigation. In a subset of cases, somatostatin receptor scintigraphy and/or positron emission tomography with 5-hydroxytryptophan was performed. Time from operation until established recurrence was recorded.

    Results:

    Tumor recurrence was established in 33 of 56 patients after a median of 32 months (range 6-217). Elevated P-CgA was the first marker to become pathologically elevated in 28 of these 33 patients (85%). In 3 of these 28 patients, radiology was simultaneously positive for a recurrence.

    Conclusion:

    P-CgA was the first marker to indicate tumor recurrence in the majority of radically operated midgut carcinoid patients. To avoid unnecessary and costly examinations in asymptomatic patients, we suggest that follow-up should comprise measurements of P-CgA twice a year and annual ultrasonography until P-CgA is elevated or clinical symptoms occur, at which time all efforts should be made to identify recurrent tumor lesions in order to give the patient the best possible treatment which, if possible, should be surgical removal of the recurrence.

  • 126. Wiedenmann, Bertram
    et al.
    Jensen, RT
    Mignon, Michel
    Modlin, I
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Doherty, G
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Preoperative diagnosis and surgical management of neuroendocrine gastroenteropancreatic tumors: general recommendation by a consensus workshop1998In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 22, no 3, p. 309-318Article in journal (Refereed)
    Abstract [en]

    In 1996 a consensus workshop on the preoperative diagnosis and surgical treatment of neuroendocrine tumor disease took place in Berlin. Although there was a consensus on the diagnosis and surgical treatment by world experts in neuroendocrine surgery in some areas, it became clear that certain management policies vary among centers. In large part, diverging policies reflect a lack of controlled studies. This paper summarizes the various opinions brought forward during this conference and emphasizes consensus approaches for the diagnosis and therapy of neuroendocrine neoplasms.

  • 127.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences. endokrin tumörbiologi.
    Pancreatic tumours as part of the MEN-1 syndrome.2005In: Best Practice & Research Clinical Endocrinology & Metabolism, Elsevier , 2005Chapter in book (Other scientific)
  • 128.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences.
    Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN12002In: Langenbeck's Archives of Surgery, Vol. 386, p. 558-569Article in journal (Refereed)
  • 129.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Department of Medical Sciences. Endokrin tumörbiologi.
    Rastad, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Familial hyperparthyroidism1994In: Current controversy in parathyroid operation adn reoperation, 1994, p. 115-130Chapter in book (Refereed)
  • 130.
    Åkerström, Göran
    et al.
    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.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Multiple Endocrine Neoplasia type 22018In: Textbook of Complex General Surgical Oncology / [ed] Shane Y Morita, Charles M Balch, V. Suzanne Klimberg, Timothy M. Pawlik, Mitchell C. Posner, Kenneth K. Tanabe, McGraw-Hill, 2018Chapter in book (Refereed)
  • 131.
    Örlefors, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Åkerström, Göran
    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.
    PET-Guided Surgery: High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours2012In: Cancers, ISSN 2072-6694, Vol. 4, no 1, p. 100-112Article in journal (Other academic)
    Abstract [en]

    Positron emission tomography (PET) with 11C-labeled 5-hydroxytryptophane (5-HTP) is a sensitive technique to visualize neuroendocrine tumours (NETs), due to high intracellular uptake of amine-precursors like L-dihydroxyphenylalanine (L-DOPA) and 5-HTP. NETs are often small and difficult to localize in spite of overt clinical symptoms due to hormonal excess. In our study, 38 consecutive NET patients underwent 11C-5-HTP-PET and morphological imaging by CT within 12 weeks prior to surgery. Surgical, histopathological and 5-HTP PET findings were correlated. 11C-5-HTP-PET corresponded to the surgical findings in 31 cases, was false negative in six, and true negative in one case resulting in 83.8% sensitivity and 100% specificity. Positive predicted value was 100%. In 11 patients 11C-5-HTP-PET was the only imaging method applied to localize the tumour. Thus, we could demonstrate that functional imaging by 11C-5-HTP-PET in many cases adds vital preoperative diagnostic information and in more than every fourth patient was the only imaging method that will guide the surgeon in finding the NET-lesion. Although the present results demonstrates that 11C-5-HTP may be used as an universal NET tracer, the sensitivity to visualize benign insulinomas and non functioning pancreatic NETs was lower.

  • 132.
    Örlefors, Håkan
    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 Radiology, Oncology and Radiation Science, Radiology.
    Garske, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Endokrin tumörbiologi.
    Långstrom, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    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.
    Whole-Body 11C-5-Hydroxytryptophan Positron Emission Tomography as a Universal Imaging Technique for Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and Computed Tomography2005In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 90, no 6, p. 3392-3400Article in journal (Refereed)
123 101 - 132 of 132
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