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  • 1.
    Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Karakatsanis, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stuart, Heather C.
    Division of Surgical Oncology, University of Miami, Florida, USA.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Association of a Prophylactic surgical approach to Stage IV Small Intestinal Neuroendocrine Tumors with Survival.2018In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 2, p. 183-189Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

    Exposure: PUSCO vs DSANCO.

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

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

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

     

  • 2.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hessman, Ola
    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.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 6, p. 741-746Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor receptor (PDGFR) beta signaling is involved in autocrine growth stimulation of tumor cells, tumor angiogenesis and regulation of tumor interstitial fluid pressure. Development of PDGFR antagonists has further increased the interest for PDGFR as targets for anticancer treatments. Malignant endocrine pancreatic tumors (EPTs) express PDGFR beta both in stroma and on tumor cells. To investigate the role of PDGFR beta signaling in EPTs we compared PDGFR beta expression in normal endocrine pancreas to malignant EPTs and metastases. PDGFR beta expression was examined by immunohistochemistry using specific polyclonal antibodies in ten tissue samples from normal endocrine pancreas, 21 from primary EPTs and 19 from metastases. In eight patients we compared the expression in normal endocrine pancreas to the corresponding primary tumor and metastases, in two patients normal tissue to the primary tumor and in 11 patients primary tumors to the corresponding metastases. Six of ten tissues containing normal pancreas stained negative for PDGFR beta on endocrine cells, while seven of ten stained positive in the stroma. Eighteen of 21 (86%) primary tumors stained positive for PDGFR beta on tumor cells and all had positive stroma stainings. All 19 metastases stained positive for PDGFR beta on tumor cells and in evaluable stroma (n=16). We have found that PDGFR beta is more frequently expressed in primary EPTs and metastases as compared to normal endocrine pancreatic tissue. This is also true for PDGFR beta expression in the corresponding stroma. We suggest that new therapeutic options to inhibit the growth and spread of EPTs could include targeting of PDGFR beta.

  • 3.
    Fyrsten, Ellen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    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.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Long-Term Surveillance of Treated Hyperparathyroidism for Multiple Endocrine Neoplasia Type 1: Recurrence or Hypoparathyroidism?2016In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 3, p. 615-621Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is surgically treated with either a subtotal parathyroidectomy removing 3 or 3,5 glands (SPX), less than 3 glands (LSPX), or a total parathyroidectomy with autotransplantation (TPX). Previous studies with shorter follow-up have shown that LSPX and SPX are associated with recurrent HPT, and TPX with hypocalcemia and substitution therapy. We examined the situation after long-term follow-up (median 20,6 years).

    METHODS: Sixty-nine patients with MEN1 HPT underwent 110 operations, the first operation being 31 LSPX, 30 SPX, and 8 TPX. Thirty patients underwent reoperative surgery in median 120 months later, as completion to TPX (n = 12), completion of LSPX to SPX (n = 9), extirpation of single glands (n = 3) still resulting in LSPX, and resection of forearm grafts (n = 3). Nine patients underwent a second, and 2 a third reoperation. In 24 patients genetic testing confirmed MEN1, and in the remaining heredity and phenotype led to the diagnosis.

    RESULTS: TPX had higher risk for hypoparathyroidism necessitating substitution therapy, at latest follow-up 50 %, compared to SPX (16 % after 3-6 months; none at latest follow-up). Recurrent HPT was common after LSPX, leading to 24 reoperations in 17 patients. No need for substitution therapy after SPX indicated forthcoming recurrent disease. Not having hypocalcemia in the postoperative period and less radical surgery than TPX were significantly associated to risk for recurrence. Further, mutation in exon 3 in the MEN1 gene may eventually be linked to risk of recurrence.

    CONCLUSION: LSPX is highly associated with recurrence and TPX with continuous hypoparathyroidism, also after long-term follow-up. SPX should be the chosen method in the majority of patients with MEN1 HPT.

  • 4.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    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.
    Hennings, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses2010In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 34, no 6, p. 1373-1379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.

  • 5.
    Hellman, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Linder, F
    Hennings, Joakim
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Barbro
    Department of Medical Sciences. Department of Medical Sciences.
    Örlefors, Håkan
    Åkerström, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Bilateral adrenalectomy for ectopic Cushing syndrome -: discussions on technique and indication2006In: World J Surg, Vol. 30, no 5, p. 909-916Article in journal (Refereed)
  • 6.
    Hessman, Ola
    et al.
    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 Medical Sciences.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Multiple allelic deletions and intratumoral genetic heterogeneity in MEN1 pancreatic tumors2001In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 86, no 3, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple tumors of the endocrine pancreas, the parathyroid, the pituitary, and other tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1 tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of 23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1 patients. Multiple allelic deletions were found. Fractional allelic loss varied from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11, whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over 30%. Different lesions from individual patients had discrepant patterns of LOH. Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in most tumor cells, whereas other chromosomal loci were deleted in portions of the analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients with malignant features. Fractional allelic loss did not correlate to malignancy or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to maintain DNA integrity and demonstrate signs of chromosomal instability.

  • 7.
    Hessman, Ola
    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.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Garske, Ulrike
    Rudberg, Claes
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    High success rate of parathyroid reoperation may be achieved with improved localization diagnosis2008In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 32, no 5, p. 774-81; discussion 782Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery, preoperative imaging studies have been increasingly adopted. We report the use of consistently applied localization diagnosis to yield high success rates in parathyroid reoperations. METHODS: Parathyroid reoperation was performed after previous parathyroid surgery in 144 patients with nonmalignant hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients who underwent parathyroid reoperation and 14 patients who were subjected to thyroid surgery before primary parathyroid operation were investigated with sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was considered adequate, additional studies were generally not obtained. RESULTS: Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all patients with previous parathyroid surgery. In patients operated from year 2000, MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and 87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q-PTH analyses provided accurate localization or regionalization in 11 of 11 recently selected patients. Q-PTH analyses in fine-needle aspirations verified parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide when operations could be terminated. In patients subjected to the algorithm of imaging procedures, reversal of hypercalcemia and apparent cure was obtained after the reoperation in 45 of 46 patients with previous parathyroid surgery, implying a success rate of 98%, and in all patients with previous thyroid surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can be improved by consistently applied sensitive methods of preoperative imaging, and reoperative procedures may then achieve nearly the same success rates as primary operations.

  • 8.
    Lindberg, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Cyclin-dependent kinase 4 (CDK4) expression in pancreatic endocrine tumors2007In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 86, no 2, p. 112-118Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Pancreatic endocrine tumors (PETs) occur sporadically, in association with the multiple endocrine neoplasia type 1 (MEN1) and the von Hippel-Lindau syndromes. CDK4 is central to the cell cycle control in pancreatic cells, and we have assessed whether CDK4 expression is deregulated in 18 human sporadic or familial PETs. Methods: Real-time quantitative PCR, immunohistochemistry, DNA sequencing, and Western blot analysis were used. Results: CDK4 mRNA was expressed in all PETs within the range of the arbitrary control. CDK4 protein was absent in normal pancreatic islets but distinctly expressed in all PETs as determined by immunohistochemistry. CDK4 expression was confirmed by Western blot analysis. No significant differences of CDK4 expression were observed between the groups of benign and malignant PETs or between tumors with or without MEN1 gene mutations. CDK4 expression was not due to gene amplification, and no mutations were identified in coding exons and RNA splice sites. c-Myc is known to be overexpressed in PETs and directly augments CDK4 expression in other cell types. Analysis of consecutive tissue sections for CDK4 and c-Myc showed overlapping homo- or heterogeneous immunostaining in all 18 PETs. Conclusion: We conclude that CDK4 and c-Myc is generally expressed in benign and malignant PETs, and regardless of MEN1 mutation-al status. Targeting of CDK4 may present an alternative to traditional chemotherapy of PETs in the future.

  • 9.
    Lollgen, R
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Szabo, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Chromosome 18 deletions are common events in midgut carcinoid tumors.2001In: Int J Cancer, Vol. 92, p. 812-Article in journal (Refereed)
  • 10.
    Lundstam, Karolina
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Radiol,Inst Clin Sci, Gothenburg, Sweden..
    Heck, Ansgar
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Godang, Kristin
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Mollerup, Charlotte
    Copenhagen Univ Hosp, Ctr HOC, Clin Breast & Endocrine Surg, Rigshosp, Copenhagen, Denmark..
    Baranowski, Marek
    St Olavs Hosp, Trondheim, Norway..
    Pernow, Ylva
    Karolinska Univ Hosp, Karolinska Inst, Dept Endocrinol, Dept Mol Med & Surg, Stockholm, Sweden..
    Aas, Turid
    Haukeland Hosp, Dept Breast & Endocrine Surg, Bergen, Norway..
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rosen, Thord
    Sahlgrens Univ Hosp, Dept Med, Sect Endocrinol Diabet & Metab, Gothenburg, Sweden..
    Nordenstrom, Jorgen
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Jansson, Svante
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Surg,Inst Clin Sci, Gothenburg, Sweden..
    Hellstrom, Mikael
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Radiol,Inst Clin Sci, Gothenburg, Sweden..
    Bollerslev, Jens
    Oslo Univ Hosp, Sect Specialized Endocrinol, Pb 4950, N-0424 Oslo, Norway.;Univ Oslo, Fac Med, Pb 4950, N-0424 Oslo, Norway..
    Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study)2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 9, p. 1907-1914Article in journal (Refereed)
    Abstract [en]

    Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm(2) and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p<0.001) and CTX-1 (p<0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm(2)) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p<0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p<0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm(2)) for all compartments (FN, p<0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p<0.001) with the exception of the LS, whereBMDwas stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT.

  • 11. Lundstam, Karolina
    et al.
    Heck, Ansgar
    Mollerup, Charlotte
    Godang, Kristin
    Baranowski, Marek
    Pernow, Ylva
    Varhaug, Jan Erik
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rosen, Thord
    Nordenstrom, Jorgen
    Jansson, Svante
    Hellstrom, Mikael
    Bollerslev, Jens
    Effects of Parathyroidectomy Versus Observation on the Development of Vertebral Fractures in Mild Primary Hyperparathyroidism2015In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 4, p. 1359-1367Article in journal (Refereed)
    Abstract [en]

    Context: Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. Objective: To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. Design: Prospective, randomized controlled study (SIPH study), with a 5-year follow-up. Setting: The study was conducted at multicenter, tertiary referral centers. Patients: Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, with a mean age at inclusion of 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). Intervention: Parathyroidectomy vs observation. Main outcome measures: Biochemistry, BMD, and new radiographic vertebral fractures. Results: Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P < .02). After surgery, BMDZ-scores increased significantly in both compartments (P < .02 for both), with a highly significant treatment effect of surgery compared to observation (P < .001). During follow-up, five new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P = .058). Conclusion: Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.

  • 12.
    Norlén, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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.
    Prophylactic Cholecystectomy in Midgut Carcinoid Patients2010In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 34, no 6, p. 1361-1367Article in journal (Refereed)
    Abstract [en]

    Patients with midgut carcinoid (MGC) tumors are commonly treated with somatostatin analogs. Adverse effects of these drugs include impairment of gallbladder function, formation of gallstones, and cholecystitis. Prophylactic cholecystectomy has been advocated, but data to support this recommendation are sparse. We have analyzed a cohort of 235 patients with MGC focusing on the risk for gallstone formation and complications thereof. Forty-eight of the 235 patients had been cholecystectomized before surgery for MGC. Of the remaining 187 patients, 144 were treated with somatostatin analogs. Eighteen of the 187 patients had their gall bladder removed during the primary carcinoid surgery. Twenty-two of the 144 somatostatin-analog-treated patients developed complications, such as gallbladder empyema (n = 1), cholangitis (n = 2), acute cholecystitis (n = 6), acute pancreatitis (n = 1) or acute pancreatitis and cholecystitis (n = 1), or biliary colic (n = 11). Ninety-two of the 144 were examined during surgery, by computed tomography, or by ultrasound, most for reasons other than gallbladder-related indications, and 63% (58/92) of these examinations revealed gallstones. Of the 43 patients not treated with somatostatin analogs, only 3 patients suffered from biliary colic and underwent cholecystectomy. In our study the incidence of gallstone-related complications seems to be higher than in the general population. We recommend that prophylactic cholecystectomy is liberally performed during laparotomy for MGC if patients are planned to undergo treatment with somatostatin analogs.

  • 13.
    Norlén, Olov
    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.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Long-Term Results of Surgery for Small Intestinal Neuroendocrine Tumors at a Tertiary Referral Center2012In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 36, no 6, p. 1419-1431Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients.

    MATERIAL AND METHODS:

    We included 603 consecutive patients (325 men; age at diagnosis 63 ± 11 years [mean ± SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra-abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery.

    RESULTS:

    Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205).

    CONCLUSIONS:

    For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.

  • 14.
    Salem, F. A.
    et al.
    Lund Univ, Dept Clin Sci, Lund, Sweden;Skane Univ Hosp, S-22185 Lund, Sweden.
    Almquist, M.
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Nordenström, E.
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Dahlberg, J.
    Sahlgrens Univ Hosp, Dept Endocrine Surg, Gothenburg, Sweden.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, C. I.
    Karolinska Univ Hosp, Dept Endocrine Surg, Stockholm, Sweden.
    Bergenfelz, A.
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    A Nested Case-Control Study on the Risk of Surgical Site Infection After Thyroid Surgery2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 8, p. 2454-2461Article in journal (Refereed)
    Abstract [en]

    It is unclear if antibiotic prophylaxis reduces the risk of surgical site infection (SSI) in thyroid surgery. This study assessed risk factors for SSI and antibiotic prophylaxis in subgroups of patients. A nested case-control study on patients registered in the Swedish National Register for Endocrine Surgery was performed. Patients with SSI were matched 1:1 by age and gender to controls. Additional information on patients with SSI and controls was queried from attending surgeons using a questionnaire. Risk factors for SSI were evaluated by logistic regression analysis and presented as odds ratio (OR) with 95% confidence interval (CI). There were 9494 operations; 109 (1.2%) patients had SSI. Patients with SSI were older (median 53 vs. 49 years) than patients without SSI p = 0.01 and more often had a cancer diagnosis 23 (21.1%) versus 1137 (12.1%) p = 0.01. In the analysis of patients with SSI versus controls, patients with SSI more often had post-operative drainage 68 (62.4%) versus 46 (42.2%) p = 0.01 and lymph node surgery 40 (36.7%) versus 14 (13.0%) p < 0.01, and both were independent risk factors for SSI, drain OR 1.82 (CI 1.04-3.18) and lymph node dissection, OR 3.22 (95% CI 1.32-7.82). A higher number of 26(62%) patients with independent risk factors for SSI and diagnosed with SSI did not receive antibiotic prophylaxis. Data were missing for 8 (31%) patients. Lymph node dissection and drain are independent risk factors for SSI after thyroidectomy. Antibiotic prophylaxis might be considered in patients with these risk factors.

  • 15.
    Segersten, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kaae Holm, Pernille
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nordgren, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Binderup, Lise
    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.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    25-hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-hydroxylated vitamin D analogue2005In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 7, p. R980-R986Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.

    METHODS:

    The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.

    RESULTS:

    1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3.

    CONCLUSION:

    These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed.

  • 16.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gastrointestinal carcinoids2005In: Endocrine Surgery, Elsevier Ltd Edinburgh , 2005, p. 163-197Chapter in book (Other scientific)
  • 17.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Midgut carcinoid tumours: surgical treatment and prognosis2005In: Best Pract Res Clin Gastroenterol, Vol. 19, p. 717-728Article in journal (Refereed)
  • 18.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Osmak, Liliana
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Management of midgut carcinoids2005In: J Surg Oncol, Vol. 89, no 3, p. 161-169Article in journal (Other (popular scientific, debate etc.))
  • 19.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Osmak, Liliana
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Surgical treatment of endocrine pancreatic tumours2004In: Neuroendocrinology, Vol. 80, no suppl 1, p. 62-66Article, review/survey (Other (popular scientific, debate etc.))
  • 20.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Segersten, Ulrika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Westin, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Parathyroid glands in calcium regulation and human disease2005In: Trends in Comparative Endocrinology and Neurobiology, ISSN 0077-8923, Vol. 1040, p. 53-58Article, review/survey (Other (popular scientific, debate etc.))
  • 21.
    Åkerström, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hessman, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Carcinoid tumors2004In: A Companion to Specialist Surgical Practice: Endocrine Surgery, Elsevier Ltd Edinburgh , 2004Chapter in book (Other scientific)
  • 22.
    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)
  • 23.
    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)
  • 24.
    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.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Remedial Parathyroid Surgery2012In: Surgery of the Thyroid and Parathyroid Glands / [ed] D. Oertli, R. Udelsman, Springer Berlin/Heidelberg, 2012, 2, p. 555-577Chapter in book (Refereed)
1 - 24 of 24
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