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  • 201.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hånell, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Björk, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Mir, Anis K.
    Gram, Hermann
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Neutralization of interleukin-1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice2009In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 30, no 3, p. 385-396Article in journal (Refereed)
    Abstract [en]

    Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.

  • 202.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat2008In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 25, no 12, p. 1449-1457Article in journal (Refereed)
    Abstract [en]

    Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models of ischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenous infusion of NXY-059 or vehicle was initiated 30min following a severe lateral fluid percussion brain injury (FPI) in adult rats (n=22), and histological and behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated in the Morris water maze at post-injury days 11–14, followed by a probe trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated protein (MAP)–2stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatial learning deficits when compared to the brain-injured, vehicle-treated control animals (p<0.05). NXY-059-treated animals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0±11mm3 versus 74.4±19mm3, respectively; p<0.01). The results show that post-injury treatment with NXY-059 significantly attenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role for ROS in the pathophysiology of TBI.

  • 203. Clementsson Kockum, Christina
    et al.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Blåsextrofi, epispadi och kloakexstrofi2015In: Grottes Barnkirurgi och Barnurologi / [ed] Christofferson R, Läckgren S, Stenberg A, Lund: Studentlitteratur AB, 2015, 1, p. 225-230Chapter in book (Other academic)
  • 204.
    Coelho, Ruben
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Ekberg, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Mani, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Rodriguez-Lorenzo, Andres
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Reconstruction of late esophagus perforation after anterior cervical spine fusion with an adipofascial anterolateral thigh free flap: A case report.2017In: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 37, no 6, p. 684-688Article in journal (Refereed)
    Abstract [en]

    Reconstruction of late esophageal perforation usually requires flap surgery to achieve wound healing. However, restoring the continuity between the digestive tract and retropharyngeal space to allow for normal swallowing remains a technical challenge. In this report, we describe the use of a thin and pliable free adipofascial anterolateral thigh (ALT) flap in a 47-year-old tetraplegic man with a history of C5-C6 fracture presented with a large posterior esophagus wall perforation allowing an easier flap insetting for a successful wound closure. The postoperative course was uneventful and mucosalization of the flap was confirmed by esophagoscopy 4 weeks postsurgery. The patient tolerated normal diet and maintained normal swallowing during a follow-up of 3 years postoperatively. The adipofascial ALT flap may provide easier insetting due to the thin and pliable layer of adipofascial tissue for reconstructing large defects of the posterior wall of the esophagus by filling the retroesophageal space.

  • 205.
    Collin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jung, B.
    Nilsson, E.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Folkesson, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Impact of mechanical bowel preparation on survival after colonic cancer resection2014In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 101, no 12, p. 1594-1600Article in journal (Refereed)
    Abstract [en]

    Background: A randomized study in 1999-2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. Methods: The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. Results: Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17.9 per cent) of 448 patients in the MBP group and 88 (22.5 per cent) of 391 in the no-MBP group developed a cancer recurrence (P = 0.093). The 10-year cancer-specific survival rate was 84.1 per cent in the MBP group and 78.0 per cent in the no-MBP group (P = 0.019). Overall survival rates were 58.8 and 56.0 per cent respectively (P = 0.186). Conclusion: Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years.

  • 206.
    Conte, Michael S.
    et al.
    Univ Calif San Francisco, Div Vasc & Endovasc Surg, 400 Parnassus Ave,Ste A581, San Francisco, CA 94143 USA.
    Bradbury, Andrew W.
    Univ Birmingham, Dept Vasc Surg, Birmingham, W Midlands, England.
    Kolh, Philippe
    Univ Hosp Liege, Dept Biomed & Preclin Sci, Wallonia, Belgium.
    White, John, V
    Advocate Lutheran Gen Hosp, Dept Surg, Niles, IL USA.
    Dick, Florian
    Kantonsspital St Gallen, Dept Vasc Surg, St Gallen, Switzerland;Univ Bern, Bern, Switzerland.
    Fitridge, Robert
    Univ Adelaide, Med Sch, Dept Vasc & Endovasc Surg, Adelaide, SA, Australia.
    Mills, Joseph L.
    Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA.
    Ricco, Jean-Baptiste
    Univ Hosp Poitiers, Dept Clin Res, Poitiers, France.
    Suresh, Kalkunte R.
    Jain Inst Vasc Sci, Bangalore, Karnataka, India.
    Murad, M. Hassan
    Mayo Clin, Evidence Based Practice Ctr, Rochester, MN USA.
    Aboyans, Victor
    Univ Hosp, Dept Cardiol, Dupuytren, France.
    Aksoy, Murat
    Amer Hosp, Dept Vasc Surg, Istanbul, Turkey.
    Alexandrescu, Vlad-Adrian
    Univ Liege, CHU Sart Tilman Hosp, Liege, Belgium.
    Armstrong, David
    Univ Southern Calif, Los Angeles, CA USA.
    Azuma, Nobuyoshi
    Asahikawa Med Univ, Asahikawa, Hokkaido, Japan.
    Belch, Jill
    Univ Dundee, Ninewells Hosp, Dundee, Scotland.
    Bergoeing, Michel
    Pontificia Univ Catolica Chile, Escuela Med, Santiago, Chile.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Chakfe, Nabil
    Univ Hosp Strasbourg, Strasbourg, France.
    Cheng, Stephen
    Univ Hong Kong, Hong Kong, Peoples R China.
    Dawson, Joseph
    Royal Adelaide Hosp, Adelaide, SA, Australia;Univ Adelaide, Adelaide, SA, Australia.
    Debus, Eike S.
    Univ Hosp Hamburg Eppendorf, Univ Heart Ctr Hamburg, Hamburg, Germany.
    Dueck, Andrew
    Univ Toronto, Schulich Heart Ctr, Sci Ctr, Sunnybrook Hlth, Toronto, ON, Canada.
    Duval, Susan
    Univ Minnesota, Med Sch, Cardiovasc Div, Minneapolis, MN 55455 USA.
    Eckstein, Hans H.
    Tech Univ Munich, Munich, Germany.
    Ferraresi, Roberto
    Ist Clin, Intervent Cardiovasc Unit, Cardiol Dept, Milan, Italy.
    Gambhir, Raghvinder
    Kings Coll Hosp London, London, England.
    Garguilo, Mauro
    Univ Bologna, Diagnost & Sperimentale, Bologna, Italy.
    Geraghty, Patrick
    Washington Univ, Sch Med, St Louis, MO USA.
    Goode, Steve
    Sheffield Vasc Inst, Sheffield, S Yorkshire, England.
    Gray, Bruce
    Greenville Hlth Syst, Greenville, SC USA.
    Guo, Wei
    301 Gen Hosp PLA, Beijing, Peoples R China.
    Gupta, Prem C.
    Care Hosp, Banjara Hills, Hyderabad, India.
    Hinchliffe, Robert
    Univ Bristol, Bristol, Avon, England.
    Jetty, Prasad
    Ottawa Hosp, Div Vasc & Endovasc Surg, Ottawa, ON, Canada;Univ Ottawa, Ottawa, ON, Canada.
    Komori, Kimihiro
    Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan.
    Lavery, Lawrence
    UT Southwestern Med Ctr, Dallas, TX USA.
    Liang, Wei
    Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai, Peoples R China.
    Lookstein, Robert
    Icahn Sch Med Mt Sinai, Div Vasc & Intervent Radiol, New York, NY 10029 USA.
    Menard, Matthew
    Brigham & Womens Hosp, Boston, MA 02115 USA.
    Misra, Sanjay
    Mayo Clin, Rochester, MN USA.
    Miyata, Tetsuro
    Sanno Hosp, Tokyo, Japan;Sanno Med Ctr, Tokyo, Japan.
    Moneta, Greg
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
    Prado, Jose A. Munoa
    Clin Venart, Tuxtla Gutierrez, Mexico.
    Munoz, Alberto
    Colombia Natl Univ, Bogota, Colombia.
    Paolini, Juan E.
    Univ Buenos Aires, Sanatoria Dr Julio Mendez, Buenos Aires, DF, Argentina.
    Patel, Manesh
    Duke Univ Hlth Syst, Div Cardiol, Durham, NC USA.
    Pomposelli, Frank
    St Elizabeths Med Ctr, Boston, MA USA.
    Powell, Richard
    Dartmouth Hitchcock, Lebanon, NH USA.
    Robless, Peter
    Mt Elizabeth Hosp, Singapore, Singapore.
    Rogers, Lee
    Amputat Prevent Ctr Amer, White Plains, NY USA.
    Schanzer, Andres
    Univ Massachusetts, Amherst, MA 01003 USA.
    Schneider, Peter
    Kaiser Fdn Hosp Honolulu, Honolulu, HI USA;Hawaii Permanente Med Grp, Kahului, HI USA.
    Taylor, Spence
    USC Sch Med Greenville, Greenville Hlth Ctr, Greenville, SC USA.
    De Ceniga, Melina, V
    Hosp Galdakao Usansolo, Bizkaia, Spain.
    Veller, Martin
    Univ Witwatersrand, Johannesburg, South Africa.
    Vermassen, Frank
    Ghent Univ Hosp, Ghent, Belgium.
    Wang, Jinsong
    Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.
    Wang, Shenming
    Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.
    Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia2019In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 58, no 1, p. S1-S109Article in journal (Refereed)
    Abstract [en]

    Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

  • 207.
    Corell, Alba
    et al.
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Carstam, L
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Henriksson, R
    Regional Cancer Centre Stockholm, Gotland, Sweden; Department of Radiation Science and Oncology, University hospital, Umeå, Sweden.
    Jakola, A S
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden; Department of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway.
    Age and surgical outcome of low-grade glioma in Sweden2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 359-368Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low-grade gliomas (LGG) are slow-growing primary brain tumors that typically affect young adults. Advanced age is widely recognized as a poor prognostic factor in LGG. The impact of age on postoperative outcome in this patient group has not been systemically studied.

    METHODS: We performed a nationwide register-based study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with a supratentorial LGG (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) during 2005-2015. Patient- and tumor-related characteristics, postoperative complications, and survival were compared between three different age groups (18-39 years, 40-59 years, and ≥60 years).

    RESULTS: We identified 548 patients; 204 patients (37.2%) aged 18-39 years, 227 patients (41.4%) aged 40-59 years, and 117 patients (21.4%) ≥60 years of age. Unfavorable preoperative prognostic factors (eg, functional status and neurological deficit) were more common with increased age (P < .001). In addition, overall survival was significantly impaired in those 60 years and above (P < .001). We observed a clear dose-response for age with separation of survival curves at 50 years. Biopsy was more common in patients ≥60 years (P < .001). Subgroup analysis of patients with resection revealed a higher amount of postoperative neurological deficits in older patients (P = .029).

    CONCLUSION: In general, older patients with LGG have several unfavorable prognostic factors compared with younger patients but seem to tolerate surgery in a comparable fashion. However, more neurological deficits were observed following resections in elderly. Our data further support a cutoff at 50 years rather than 40 years for selection of high-risk patients.

  • 208.
    Correa, Pamela
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Vitamin D and its receptor in parathyroid tumors2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Correa, P. 2002. Vitamin D and its receptor in parathyroid tumors. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1186. 49 pp. Uppsala. ISBN 91-554-541-0

    Hyperparathyroidism (HPT) is characterized by tumor development in the parathyroid glands and excessive production of parathyroid hormone. Parathyroidectomy is the only considered therapy for the majority of patients.

    LOH (loss of heterozygosity) analysis revealed putative tumor suppressor genes on chromosome regions 1p and 11q in tumors from patients with truly mild hypercalcemia.

    Active vitamin D [1,25(OH)2D3] and its receptors, the vitamin D receptor (VDR), are essential regulators of the calcium homeostasis and are involved in HPT development. The VDR-FokI polymorphism, coupled to bone mineral density, was found not to be associated to development of primary HPT (pHPT). The total VDR mRNA levels is reduced in adenomas of pHPT as well as in hyperplastic glands of secondary HPT (sHPT). The VDR exon 1f transcripts were exclusively downregulated in the adenomas of pHPT, suggesting default regulation of the tissue-specially expressed VDR 1f promoter. The cytochrome P450 enzymes responsible for synthesis and degradation of 1,25(OH)2D3, namely vitamin D3 25-hydroxylase (25-hydroxylase), 25-hydroxyvitamin D3 1a-hydroxylase (1a-hydroxylase) and 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) were found to be expressed in normal and pathological parathyroid glands. Tumors of pHPT and sHPT demonstrated increased 1a-hydroxylase and reduced 24- and 25-hydroxylase expression, suggesting an augmented local production of active vitamin D. In contrast, parathyroid carcinomas displayed reduced expression of all three hydroxylases. The gained knowledge of vitamin D metabolism and catabolism in parathyroid tumors may indicate possibilities for novel treatment of sHPT and perhaps pHPT.

  • 209.
    Cristóbal, Lara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Linder, Sora
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Lopez, Beatriz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Mani, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Rodriguez-Lorenzo, Andres
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Free anterolateral thigh flap and masseter nerve transfer for reconstruction of extensive periauricular defects: Surgical technique and clinical outcomes2017In: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 37, no 6, p. 479-486Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Radical tumor ablation in the periauricular area often results in extensive soft tissue defects, including facial nerve sacrifice, bone and/or dura defects. Reconstruction of these defects should aim at restoring facial reanimation, wound closure, and facial and neck contours. We present our experience using free anterolateral thigh flap (ALT) in combination with masseter nerve to facial nerve transfer in managing complex defects in the periauricular area.

    METHODS: Between 2011 and 2015 six patients underwent a combined procedure of ALT flap reconstruction and masseter nerve transfer, to reconstruct extensive, post tumor resection, periauricular defects. The ALT flap was customized according to the defect. For smile restoration, the masseter nerve was transferred to the buccal branch of the facial nerve. If the facial nerve stump was preserved, interposition of nerve grafts to the zygomatic and frontal branches was performed to provide separate eye closure. The outcomes were analyzed by assessing wound closure, contour deformity, symmetry of the face, and facial nerve function.

    RESULTS: There were no partial or total flap losses. Stable wound closure and adequate volume replacement in the neck was achieved in all cases, as well as good facial tonus and symmetry. The mean follow-up time of clinical outcomes was 16.8 months. Smile restoration was graded as good or excellent in four cases, moderate in one and fair in one.

    CONCLUSION: Extensive periauricular defects following oncologic resection could be adequately reconstructed in a combined procedure of free ALT flap and masseter nerve transfer to the facial nerve for smile restoration.

  • 210.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Maharjan, Rajani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Delgado Verdugo, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Stålberg, Peter
    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, Endocrine Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    MAX mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours2014In: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 13, no 1, p. 121-125Article in journal (Refereed)
    Abstract [en]

    Pheochromocytoma (PCC) and Paraganglioma are rare tumours originating from neuroendocrine cells. Up to 60 % of cases have either germline or somatic mutation in one of eleven described susceptibility loci, SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127 and MYC associated factor-X (MAX). Recently, germline mutations in MAX were found to confer susceptibility to PCC and paraganglioma (PGL). A subsequent multicentre study found about 1 % of PCCs and PGLs to have germline or somatic mutations in MAX. However, there has been no study investigating the frequency of MAX mutations in a Scandinavian cohort. We analysed tumour specimens from 63 patients with PCC and PGL treated at Uppsala University hospital, Sweden, for re-sequencing of MAX using automated Sanger sequencing. Our results show that 0 % (0/63) of tumours had mutations in MAX. Allele frequencies of known single nucleotide polymorphisms rs4902359, rs45440292, rs1957948 and rs1957949 corresponded to those available in the Single Nucleotide Polymorphism Database. We conclude that MAX mutations remain unusual events and targeted genetic screening should be considered after more common genetic events have been excluded.

  • 211.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Verdugo, Alberto Delgado
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    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.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma2013In: Endocrine connections, ISSN 2049-3614, Vol. 2, no 2, p. 104-111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of genes is constantly growing and the 11 genes together consist of 144 exons. A genetic screening test is extensively time consuming and expensive. Hence, we introduce next-generation sequencing (NGS) as a time-efficient and cost-effective alternative.

    METHODS:

    Tumour lesions from three patients with apparently sporadic PCC were subjected to whole exome sequencing utilizing Agilent Sureselect target enrichment system and Illumina Hi seq platform. Bioinformatics analysis was performed in-house using commercially available software. Variants in PCC and PGL susceptibility genes were identified.

    RESULTS:

    We have identified 16 unique genetic variants in PCC susceptibility loci in three different PCC, spending less than a 30-min hands-on, in-house time. Two patients had one unique variant each that was classified as probably and possibly pathogenic: NF1 Arg304Ter and RET Tyr791Phe. The RET variant was verified by Sanger sequencing.

    CONCLUSIONS:

    NGS can serve as a fast and cost-effective method in the clinical genetic screening of PCC. The bioinformatics analysis may be performed without expert skills. We identified process optimization, characterization of unknown variants and determination of additive effects of multiple variants as key issues to be addressed by future studies.

  • 212.
    Dafnis, George
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Colonoscopy: Introduction and development, completion rates, complications and cancer detection2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In a population-based study in the county of Södermanland, 6066 colonoscopies performed in 4304 patients from 1979 to 1995 inclusive were evaluated. As indications, bleeding increased and polyps and unclear x-ray findings decreased. Surveillance (cancer, polyps, colitis) was fairly stable. Both the rate of complete colonoscopies (overall 75%), and the proportion of colonoscopies performed by experienced endoscopists increased over time. The annual number of barium enemas was relatively constant up to 1992, but then decreased. Completion rates decreased by female sex and by age, and increased by previous colonic surgery or long-standing colitis, but remained unchanged by time period or presence of diverticulosis. Completion rates were influenced by endoscopist's experience and to some extent by intensity of colonoscopy. There was a large inter-endoscopist variation, at each level of experience, in the ability to perform complete colonoscopy, implying substantial differences in individual learning curves. The overall morbidity was 0.4%, diagnostic morbidity 0.2% and therapeutic morbidity 1.2%. Most frequent complications were bleeding (0.2%) and perforation (0. 1 %), with no colonoscopy-related mortality. Bleeding was confined to therapeutic colonoscopy and occurred immediately, mostly after removal of large thick-stalk polyps. Perforations at diagnostic colonoscopy occurred in the left colon; they were diagnosed sooner than at therapeutic colonoscopy, at which the caecum was the most frequent perforation site. Bleeding complication rate was correlated to experience of the endoscopists. Colorectal cancers were diagnosed in 174 patients and in 6 patients were not detected at colonoscopy. Comparing these, there were no significant differences in gender, age, indications, presence of polyps or diverticulosis, time period, or experience of endoscopist. The mean completion rate for the endoscopists was lower in patients with undetected cancers. Coexisting inflammatory bowel disease was more common in patients with late diagnosis. The sensitivity was 96.7%, higher when the indication was bleeding, canoer or unclear x-ray, and lower when the colonoscopy was performed on other indications.

  • 213.
    Dahlberg, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Rectal cancer: Aspects of surgery and radiotherapy1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In rectal cancer, local failure is one of the principle causes of morbidity and mortality. The use of radiotherapy as an adjuvant treatment in resectable rectal cancer is extensively studied in order to lower unacceptably high local failure rates. Data from the literature clearly indicate that preoperative radiotherapy is superior to postoperative irradiation in reducing failure rates. Provided the dose is sufficiently high, a relative reduction in the local recurrence rate of 60% in combination with "standard" surgery is to be expected. In addition, this reduction seems to increase survival. An important and unanswered question is the role of adjuvant radiotherapy with "optimised" surgery as total mesorectal excision.

    Our data show that the results of treatment can be improved by concentration of surgery to a colorectal team. Changed primary treatment with a combination of optimised surgery and preoperative radiotherapy will further improve treatment outcome with lowered local recurrence rates and increased survival. With proper radiation technique, the acute-subacute toxicity can be kept acceptably low and besides bowel dysfunction, no evidence of substantial late adverse effects have been found.

    The cost-effectiveness of preoperative radiotherapy is in accordance with other well-accepted medical interventions.

  • 214.
    Dahlstrand, Ursula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Femoral and Inguinal Hernia: How to Minimize Adverse Outcomes Following Repair2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Groin hernia is common, and each year 200 repairs per 100 000 adult inhabitants are performed in Sweden. Groin hernias are either inguinal or femoral (2-4%). Elective repair is not associated with an excess mortality, but adverse outcomes include recurrence and long-term pain. Emergency procedures have a 4% mortality rate with an increased risk for bowel resection and postoperative complications. The aim of this thesis was to identify risk factors for adverse outcomes and to propose measures to improve groin hernia treatment.

    Twenty-three per cent of female hernias were femoral. Thirty-six per cent of femoral hernias, and 5% of inguinal hernias, have emergency procedures. Females (OR 1.47) and patients above 65 years-of-age (OR 2.24) were at higher risk for emergency repair. Bowel resection was performed in 23% of emergency femoral repairs, and the 30-day mortality was 10 times that of an age- and gender-matched population. The majority of emergency patients were unaware of their hernia, and one third had previously had no groin symptoms.

    Femoral repairs were at larger risk for recurrence than inguinal repairs. The surgical techniques with least risk for recurrence were preperitoneal mesh repairs (open HR 0.28, and laparoscopic HR 0.31). Long-term pain was present in 24% of femoral hernia patients, of whom 5.5% described pain interfering with daily activities. The only factor predicting the risk for long-term pain was pain preoperatively. Pain decreased with time.

    In a randomized study on inguinal hernia, TEP resulted in less pain six weeks after surgery than Lichtenstein repair performed under local anesthesia (LLA). TEP patients were to a larger extent able to perform sporting activities. No difference was seen in intra-operative complications.

    Femoral hernias should be given high priority for repair and preperitoneal techniques should be used. Earlier diagnosis, in the elective setting, is probably difficult to attain. Heightened awareness in the emergency department is required. TEP is safe, and results in less pain than LLA six weeks after surgery. A widening of indications for TEP in primary inguinal hernia repair is justifiable.

    List of papers
    1. Emergency Femoral Hernia Repair A Study Based on a National Register
    Open this publication in new window or tab >>Emergency Femoral Hernia Repair A Study Based on a National Register
    Show others...
    2009 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 249, no 4, p. 672-676Article in journal (Refereed) Published
    Abstract [en]

    Objective: To describe the characteristics of femoral hernias and outcome of femoral repairs, with special emphasis on emergency operations. Background: Femoral hernias account for 2% to 4% of all groin hernias. However, the lack of large-scale studies has made it impossible to draw conclusions regarding the best management of these hernias. Methods: The study is based on patients 15 years or older who underwent groin hernia repair 1992 to 2006 at units participating in the Swedish Hernia Register. Results: Three thousand nine hundred eighty femoral hernia repairs were registered, 1490 on men and 2490 on women: 1430 (35.9%) patients underwent emergency surgery compared with 4.9% of the 138,309 patients with inguinal hernias. Bowel resection was performed in 22.7% (325) of emergent femoral repairs and 5.4% (363) of emergent inguinal repairs. Women had a substantial over risk for undergoing emergency femoral surgery compared with men (40.6% vs. 28.1%). An emergency femoral hernia operation was associated with a 10-fold increased mortality risk, whereas the risk for an elective repair did not exceed that of the general population. In elective femoral hernias, laparoscopic (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67) and open preperitoneal mesh (hazard ratio, 0.28; confidence interval, 0.12-0.65) techniques resulted in fewer re-operations than suture repairs. Conclusions: Femoral hernias are more common in women and lead to a substantial over risk for an emergency operation, and consequently, a higher rate of bowel resection and mortality. Femoral hernias should be operate with high priority to avoid incarceration and be repaired with a mesh.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-129143 (URN)10.1097/SLA.0b013e31819ed943 (DOI)000264899100022 ()
    Available from: 2010-08-09 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved
    2. Chronic Pain After Femoral Hernia Repair: A Cross-Sectional Study
    Open this publication in new window or tab >>Chronic Pain After Femoral Hernia Repair: A Cross-Sectional Study
    Show others...
    2011 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 254, no 6, p. 1017-1021Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    To explore the prevalence of and to identify possible risk factors for chronic pain after surgery for femoral hernia.

    BACKGROUND:

    Chronic pain has become a very important outcome in quality assessment of inguinal hernia surgery. There are no studies on the risk for chronic pain after femoral hernia surgery.

    METHODS:

    The Inguinal Pain Questionnaire was sent to 1967 patients who had had a repair for primary unilateral femoral hernia between January 1, 1997 and December 31, 2006. A follow-up period of at least 18 months was chosen. Answers from 1461 patients were matched with data recorded in the Swedish Hernia Register and analyzed.

    RESULTS:

    Some degree of pain during the previous week was reported by 24.2% (354) of patients. Pain interfered with daily activities in 5.5% (81) of patients. Emergency surgery (OR = 0.54; 95% CI = 0.40-0.74) and longer time since surgery (OR = 0.93; 95% CI = 0.89-0.98 for each year added) were associated with lower risk for chronic postoperative pain, whereas a high level of preoperative pain was associated with a higher risk for chronic pain (OR = 1.17; 95% CI = 1.10-1.25). Surgical technique was not found to influence the risk for chronic pain in multivariate logistic regression analysis.

    CONCLUSIONS:

    Chronic postoperative pain is as important a complication after femoral hernia surgery as it is after inguinal hernia surgery. In contrast to inguinal hernia surgery, no risk factor related to surgical technique was found. Further investigations into the role of preoperative pain are necessary.

    Keywords
    hernia, chronic pain, long-term post operative pain, femoral, complication, questionnaire
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-162197 (URN)10.1097/SLA.0b013e31822ba9b6 (DOI)000297375200027 ()21862924 (PubMedID)
    Available from: 2011-11-27 Created: 2011-11-25 Last updated: 2017-12-08Bibliographically approved
    3. Little Chance of Preventing Emergency Surgery for Femoral Hernia: Symptoms and Signs Prior to Presentation are Often Not Present
    Open this publication in new window or tab >>Little Chance of Preventing Emergency Surgery for Femoral Hernia: Symptoms and Signs Prior to Presentation are Often Not Present
    2011 (English)Article in journal (Refereed) Submitted
    Keywords
    hernia, femoral hernia, emergency surgery, emergency repair, symptoms, presentation
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-162201 (URN)
    Available from: 2011-11-27 Created: 2011-11-26 Last updated: 2012-01-03Bibliographically approved
    4. TEP under General Anesthesia is Superior to Lichtenstein under Local Anesthesia in terms of Pain Six Weeks after Surgery: Results from a Randomized Trial
    Open this publication in new window or tab >>TEP under General Anesthesia is Superior to Lichtenstein under Local Anesthesia in terms of Pain Six Weeks after Surgery: Results from a Randomized Trial
    Show others...
    2012 (English)Manuscript (preprint) (Other academic)
    Keywords
    TEP, Lichtenstein, hernia, inguinal hernia, randomised, RCT, local anesthesia, postoperative pain, pain
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-162202 (URN)
    Available from: 2011-11-27 Created: 2011-11-26 Last updated: 2012-01-03
  • 215.
    Dahlstrand, Ursula
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sandblom, Gabriel
    CLINTEC, Karolinska Institutet.
    Ljungdahl, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wollert, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gunnarsson, Ulf
    CLINTEC, Karolinska Institutet.
    TEP under General Anesthesia is Superior to Lichtenstein under Local Anesthesia in terms of Pain Six Weeks after Surgery: Results from a Randomized Trial2012Manuscript (preprint) (Other academic)
  • 216.
    Dahlstrand, Ursula
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sandblom, Gabriel
    CLINTEC, Karolinska Institutet.
    Nordin, Pär
    Insitutionen för kirurgisk och perioperativ vetenskap, Umeå Universitet.
    Wollert, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gunnarsson, Ulf
    CLINTEC, Karolinska Institutet.
    Chronic Pain After Femoral Hernia Repair: A Cross-Sectional Study2011In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 254, no 6, p. 1017-1021Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To explore the prevalence of and to identify possible risk factors for chronic pain after surgery for femoral hernia.

    BACKGROUND:

    Chronic pain has become a very important outcome in quality assessment of inguinal hernia surgery. There are no studies on the risk for chronic pain after femoral hernia surgery.

    METHODS:

    The Inguinal Pain Questionnaire was sent to 1967 patients who had had a repair for primary unilateral femoral hernia between January 1, 1997 and December 31, 2006. A follow-up period of at least 18 months was chosen. Answers from 1461 patients were matched with data recorded in the Swedish Hernia Register and analyzed.

    RESULTS:

    Some degree of pain during the previous week was reported by 24.2% (354) of patients. Pain interfered with daily activities in 5.5% (81) of patients. Emergency surgery (OR = 0.54; 95% CI = 0.40-0.74) and longer time since surgery (OR = 0.93; 95% CI = 0.89-0.98 for each year added) were associated with lower risk for chronic postoperative pain, whereas a high level of preoperative pain was associated with a higher risk for chronic pain (OR = 1.17; 95% CI = 1.10-1.25). Surgical technique was not found to influence the risk for chronic pain in multivariate logistic regression analysis.

    CONCLUSIONS:

    Chronic postoperative pain is as important a complication after femoral hernia surgery as it is after inguinal hernia surgery. In contrast to inguinal hernia surgery, no risk factor related to surgical technique was found. Further investigations into the role of preoperative pain are necessary.

  • 217.
    Dahlstrand, Ursula
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sandblom, Gabriel
    Wollert, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gunnarsson, Ulf
    Limited Potential for Prevention of Emergency Surgery for Femoral Hernia2014In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 8, p. 1931-1936Article in journal (Refereed)
    Abstract [en]

    Femoral hernias are frequently operated on as an emergency. Emergency procedures for femoral hernia are associated with an almost tenfold increase in postoperative mortality, while no increase is seen for elective procedures, compared with a background population. The aim of this study was to compare whether symptoms from femoral hernias and healthcare contacts prior to surgery differ between patients who have elective and patients who have emergency surgery. A total of 1,967 individuals operated on for a femoral hernia over 1997-2006 were sent a questionnaire on symptoms experienced and contact with the healthcare system prior to surgery for their hernia. Answers were matched with data from the Swedish Hernia Register. A total of 1,441 (73.3 %) patients responded. Awareness of their hernia prior to surgery was denied by 53.3 % (231/433) of those who underwent an emergency procedure. Of the emergency operated patients, 31.3 % (135/432) negated symptoms in the affected groin prior to surgery and 22.2 % (96/432) had neither groin nor other symptoms. Elective patients had a considerably higher contact frequency with their general practitioner, as well as the surgical outpatient department, prior to surgery compared with patients undergoing emergency surgery (p < 0.001). Patients who have elective and patients who have emergency femoral hernia surgery differ in previous symptoms and healthcare contacts. Patients who need emergency surgery are often unaware of their hernia and frequently completely asymptomatic prior to incarceration. Early diagnosis and expedient surgery is warranted, but the lack of symptoms hinders earlier detection and intervention in most cases.

  • 218.
    Dahlstrand, Ursula
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sandblom, Gabriel
    CLINTEC, Karolinska Institutet.
    Wollert, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gunnarsson, Ulf
    CLINTEC, Karolinska Institutet.
    Little Chance of Preventing Emergency Surgery for Femoral Hernia: Symptoms and Signs Prior to Presentation are Often Not Present2011Article in journal (Refereed)
  • 219.
    Dalberg, Kristina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Liedberg, A
    Johansson, U
    Rutqvist, L E
    Uncontrolled local disease after salvage treatment for ipsilateral breast tumour recurrence2003In: EJSO, Vol. 29, p. 143-154Article in journal (Refereed)
  • 220.
    Danielson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Anorectal Malformations: Long-term outcome and aspects of secondary treatment2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Faecal incontinence (FI) is defined as the inability to control bowel movements. The causes of FI are many and diverse. One of the more uncommon reasons for FI is Anorectal Malformations (ARMs). An ARM is a congenital anomaly that affects somewhere between 1/2500 and 1/5000 live born babies. Many ARM patients have persistent FI. Several different procedures have been utilised to address this issue. This thesis aims to evaluate (1) the long-term outcome in adulthood of ARMs in relation to the modern Krickenbeck classification, and (2) scope for treating FI with transanal injection with dextranomer in non-animal stabilised hyaluronic acid (NASHA/Dx), in patients both with and without ARMs.

    All patients treated for ARMs in Uppsala up to 1993 were invited to participate in a questionnaire study of quality of life and function. The study included 136 patients and compared them with 136 age- and sex-matched controls. The Krickenbeck classification was found to predict functional outcome, and ARM patients had more problems with incontinence and obstipation, as well as inferior Quality of Life (QoL), compared with controls. 

    Thirty-six patients with FI, owing to causes other than ARMs, were treated with transanal submucous injection of NASHA/Dx. The patients were monitored for two years after treatment. Significant reductions in both their incontinence score and the number of their incontinence episodes were achieved.  A significant improvement in QoL was observed in patients who had at least a 75% reduction in incontinence episodes. No serious complications occurred.

    A prospective study of transanal injection of NASHA/Dx was conducted on seven patients with persistent FI after ARMs. After six months a significant reduction in the number of incontinence episodes was obtained. A significant improvement in QoL was also found. No serious complications occurred.

    In conclusion, adult patients with ARMs have inferior outcome of anorectal function and QoL compared with controls. NASHA/Dx is effective and appears to be safe in treating FI in general. This effect seems to be the same in selected patients with persistent FI after ARMs.

    List of papers
    1. Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?
    Open this publication in new window or tab >>Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?
    2017 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, no 3, p. 463-468Article in journal (Refereed) Published
    Abstract [en]

    Background/purpose

    Knowledge about the functional outcome in adults with anorectal malformations is essential to organize structured transition to adult care for this patient group. The aim of this study was to investigate the functional outcome and quality of life in adults with anorectal malformations characterized according to the Krickenbeck classification.

    Methods

    Of 256 patients diagnosed with anorectal malformations at our institution in 1961–1993, 203 patients could be traced and were invited to participate in the study. One hundred and thirty-six patients replied (67%) and were compared with one hundred and thirty-six population based sex and age-matched controls. Patients and controls were evaluated with both a validated questionnaire as well as a study-specific questionnaire to assess bowel function. SF-36 was used for quality of life. Outcome in nine incontinence-related parameters, 10 constipation-related, 6 urogenital function-related, and 13 quality of life parameters were assessed in the patients and compared to the outcome of controls as well as to the type of anorectal malformations according to the Krickenbeck classification.

    Results

    The ARM-patients had an inferior outcome (P < 0.05) for all incontinence parameters, 8 of 10 parameters for constipation, 2 of 6 for urogenital function and 7 of 13 quality of life parameters. Patients with rectobulbar and vestibular fistulas had the worst statistical outcome but patients with cloaca and rectoprostatic/bladder-neck fistula had worse outcome in absolute numbers. Forty-four patients (32%) reported incontinence of stool at least once a week and 16 (12%) had a permanent colostomy.

    Conclusions

    The functional outcome and quality of life in adults with anorectal malformations are closely related to the type of malformation. A large proportion of the patients have persistent fecal incontinence, constipation and sexual problems that have a negative influence on their quality of life. Structured multidisciplinary follow-up of adults with anorectal malformations by pediatric and colorectal surgeons, as well as urologists and gynecologists is therefore advocated.

    Keywords
    Anorectal malformations, Long term outcome, Functional outcome, Sexual outcome, Quality of life, Transition to adult care
    National Category
    Surgery
    Research subject
    Pediatric Surgery
    Identifiers
    urn:nbn:se:uu:diva-241240 (URN)10.1016/j.jpedsurg.2016.10.051 (DOI)000397964100019 ()27894765 (PubMedID)
    Available from: 2015-01-09 Created: 2015-01-09 Last updated: 2017-04-26Bibliographically approved
    2. Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence
    Open this publication in new window or tab >>Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence
    Show others...
    2009 (English)In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 6, p. 1101-1106Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: NASHA Dx gel has been used extensively for treatments in the field of urology. This study was performed to evaluate NASHA Dx gel as an injectable anal canal implant for the treatment of fecal incontinence. METHODS: Thirty-four patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were injected with 4 x 1 ml of NASHA Dx gel, just above the dentate line in the submucosal layer. The primary end point was change in the number of incontinence episodes and a treatment response was defined as a 50 percent reduction compared with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS: The median number of incontinence episodes during four weeks was 22 (range, 2 to 77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders at 6 months, compared with 19 (56 percent) at 12 months. No long-term side effects or serious adverse events were reported. CONCLUSIONS: Submucosal injection of NASHA Dx gel is an effective treatment for fecal incontinence. The effect is sustained for at least 12 months. The treatment is associated with low morbidity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-113092 (URN)10.1007/DCR.0b013e31819f5cbf (DOI)000273644400010 ()19581853 (PubMedID)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2017-12-12Bibliographically approved
    3. Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
    Open this publication in new window or tab >>Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
    2013 (English)In: Techniques in Coloproctology, ISSN 1123-6337, E-ISSN 1128-045X, Vol. 17, no 4, p. 389-395Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Stabilized non-animal hyaluronic acid/dextranomer (NASHA® Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.

    METHODS:

    Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.

    RESULTS:

    Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.

    CONCLUSIONS:

    Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-196656 (URN)10.1007/s10151-012-0949-8 (DOI)000321915700010 ()23224913 (PubMedID)
    Available from: 2013-03-12 Created: 2013-03-12 Last updated: 2017-12-06Bibliographically approved
    4. Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.
    Open this publication in new window or tab >>Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background/Purpose

    During the last decades injectable bulking therapy has emerged as a promising treatment option for fecal incontinence (FI). Very little has been published on the use of injectable bulking therapy on patients with persistent FI after anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.

    Methods

    Seven adult patients with persistent FI after ARM were treated with perianal submucuos injection of NASHA/Dx. They were evaluated preoperatively and at three and six months after treatment with a validated bowel function questionnaire and a two-week bowel diary as well as FIQL and SF-36 quality of life questionnaires.

    Results

    Before treatment mean Miller incontinence score was 13,7 and the mean number of incontinence episodes over two weeks was 20,7. At 6 months after treatment the corresponding figures were 10,7 (P=0,1088) and 5,3 (P=0,0180) respectively. No significant changes could be found in either FIQL or SF-36 scores. No serious adverse events occurred during the study.

    Conclusions

    NASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Long-term follow up of larger patient series as well as studies on patients in adolescence are needed.

     

    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-241241 (URN)
    Available from: 2015-01-09 Created: 2015-01-09 Last updated: 2015-03-09
  • 221.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Olsen, Leif
    Akad Sjukhuset, Dept Pediat Surg, S-75185 Uppsala, Sweden..
    Wester, Tomas
    Karolinska Univ Hosp, Dept Pediat Surg, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Posterior sagittal anorectoplasty results in better bowel function and quality of life in adulthood than pull-through procedures2015In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 50, no 9, p. 1556-1559Article in journal (Refereed)
    Abstract [en]

    Background/purpose: The short-term outcome of posterior sagittal anorectoplasty (PSARP) procedure has been reported to be better than after abdominoperineal or abdominosacroperineal (AP) procedures. This study aimed to investigate the long-term functional outcome and quality of life after PSARP in adulthood and compare with the outcome after AP procedures. Methods: Twenty-four patients operated with PSARP at the Department of Pediatric Surgery, Uppsala, Sweden, from 1984 to 1993 were identified. They were compared with 20 patients that underwent AP pull-through procedures from 1974 to 1983. The patients were sent validated bowel function and quality of life (SF-36) questionnaires. Sixteen PSARP (median age 21, five females) patients and fourteen AP patients (seven abdominosacroperineal and seven abdominoperineal pull-throughs, median age 32, seven females) responded and were included in the study. Results: The median Miller incontinence score was 1 (range 0-13) in the PSARP group and 10 (range 3-16) in the pull-through group (P = 0.0042). The use of underwear protection and oral loperamide was significantly less frequent in the PSARP group (P = 0.0096 and 0.0021 respectively). The SF-36 scores of Vitality, Mental health and Mental Cluster Scale were higher in the PSARP group (P = 0.0291, 0.0500, 0.0421 respectively). Conclusions: PSARP results in superior bowel function and better quality of life in adulthood compared with AP procedures for the repair of anorectal malformations.

  • 222.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wester, Tomas
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background/Purpose

    During the last decades injectable bulking therapy has emerged as a promising treatment option for fecal incontinence (FI). Very little has been published on the use of injectable bulking therapy on patients with persistent FI after anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.

    Methods

    Seven adult patients with persistent FI after ARM were treated with perianal submucuos injection of NASHA/Dx. They were evaluated preoperatively and at three and six months after treatment with a validated bowel function questionnaire and a two-week bowel diary as well as FIQL and SF-36 quality of life questionnaires.

    Results

    Before treatment mean Miller incontinence score was 13,7 and the mean number of incontinence episodes over two weeks was 20,7. At 6 months after treatment the corresponding figures were 10,7 (P=0,1088) and 5,3 (P=0,0180) respectively. No significant changes could be found in either FIQL or SF-36 scores. No serious adverse events occurred during the study.

    Conclusions

    NASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Long-term follow up of larger patient series as well as studies on patients in adolescence are needed.

     

  • 223.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wester, Tomas
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?2017In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, no 3, p. 463-468Article in journal (Refereed)
    Abstract [en]

    Background/purpose

    Knowledge about the functional outcome in adults with anorectal malformations is essential to organize structured transition to adult care for this patient group. The aim of this study was to investigate the functional outcome and quality of life in adults with anorectal malformations characterized according to the Krickenbeck classification.

    Methods

    Of 256 patients diagnosed with anorectal malformations at our institution in 1961–1993, 203 patients could be traced and were invited to participate in the study. One hundred and thirty-six patients replied (67%) and were compared with one hundred and thirty-six population based sex and age-matched controls. Patients and controls were evaluated with both a validated questionnaire as well as a study-specific questionnaire to assess bowel function. SF-36 was used for quality of life. Outcome in nine incontinence-related parameters, 10 constipation-related, 6 urogenital function-related, and 13 quality of life parameters were assessed in the patients and compared to the outcome of controls as well as to the type of anorectal malformations according to the Krickenbeck classification.

    Results

    The ARM-patients had an inferior outcome (P < 0.05) for all incontinence parameters, 8 of 10 parameters for constipation, 2 of 6 for urogenital function and 7 of 13 quality of life parameters. Patients with rectobulbar and vestibular fistulas had the worst statistical outcome but patients with cloaca and rectoprostatic/bladder-neck fistula had worse outcome in absolute numbers. Forty-four patients (32%) reported incontinence of stool at least once a week and 16 (12%) had a permanent colostomy.

    Conclusions

    The functional outcome and quality of life in adults with anorectal malformations are closely related to the type of malformation. A large proportion of the patients have persistent fecal incontinence, constipation and sexual problems that have a negative influence on their quality of life. Structured multidisciplinary follow-up of adults with anorectal malformations by pediatric and colorectal surgeons, as well as urologists and gynecologists is therefore advocated.

  • 224.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wester, Tomas
    Karolinska Univ Hosp, Dept Pediat Surg, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Persistent fecal incontinence into adulthood after repair of anorectal malformations2019In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 34, no 3, p. 551-554Article in journal (Refereed)
    Abstract [en]

    Purpose: Persistent fecal incontinence beyond childhood is common in ARM patients. The aim of this study was to analyze a consecutive series of adult patients with persistent incontinence, establish the causes, and evaluate whether further treatment could be offered. Methods: Forty-four adult ARM patients with reported incontinence were invited. Eighteen patients (11 males, median age 40.5 years, range 18-50 years) accepted and underwent clinical examination, rectoscopy, and 3D-ultrasound. Five had previously been treated with secondary surgery to improve continence. Results: Seventeen of the 18 patients had abnormal findings at examination. Eight patients had obstruction of the reconstructed anus. Eleven patients had sacral deformities. Nine patients had a defect in the external anal sphincter and nine patients could not contract the sphincter on demand. Five patients had significant prolapse of mucosa. In one patient, the neoanus was totally misplaced, one patient had a rectovaginal fistula, and one patient had short bowel syndrome due to several small bowel resections. Ten patients were offered conservative and five surgical treatment. Conclusions: This case series of adults shows that a majority of the patients can be offered further treatment. This indicates a need for structured follow-up of ARM patients into adulthood.

  • 225.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wester, Tomas
    Astrid Lindgren Childrens Hosp, Dept Pediat Surg, Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Long-Term Outcome after Dynamic Graciloplasty for Treatment of Persistent Fecal Incontinence in Patients with Anorectal Malformations2019In: European journal of pediatric surgery, ISSN 0939-7248, E-ISSN 1439-359X, Vol. 29, no 3, p. 276-281Article in journal (Refereed)
    Abstract [en]

    Purpose Dynamic graciloplasty (DGP) has been used to treat severe fecal incontinence since the 1980s. Previous studies have shown an inferior outcome in patients with anorectal malformations (ARMs). Our experience has been that DGP has been appreciated by ARM -patients. The objective of the study was to evaluate the long-term outcome of DGP in our patients with ARM compared with patients with other underlying conditions. Materials and Methods Twenty-three patients operated with DGP at our institution from 1996 to 2010 were sent validated bowel function and quality of life questionnaires. Eighteen of 23 responded. Seven had ARM and 11 had other etiologies of fecal incontinence. The mean follow-up time was 11.6 years (range, 5-17). Results Four of 7 of the patients with ARM and 8 of 11 of patients with other etiologies used their implants at follow-up. The Miller incontinence score was slightly higher for patients with ARMs, but they had less constipation and higher Fecal Incontinence Quality of Life (FIQL)- and 36-Item Short Form Health Survey (SF-36) scores. None of the differences were statistically significant. Conclusion This study cannot confirm earlier reports in which DGP has an inferior outcome in patients with ARM. We therefore believe that the procedure should remain a treatment option for selected patients.

  • 226. Danielsson, Par A
    et al.
    Fredriksson, Camilla
    Huss, Fredrik
    A Novel Concept for Treating Large Necrotizing Fasciitis Wounds With Bilayer Dermal Matrix, Split-thickness Skin Grafts, and Negative Pressure Wound Therapy.2009In: Wounds (King of Prussia, Pa.), ISSN 1044-7946, E-ISSN 1943-2704, Vol. 21, no 8Article in journal (Refereed)
    Abstract [en]

    Treatment of necrotizing fasciitis (NF) includes radical surgical debridement often resulting in large wounds that need to be closed with methods including split-thickness skin grafts (STSG), local flaps, or guided tissue regeneration procedures. In this case report, a 45 year-old Caucasian male was surgically treated for a benign left groin hernia, developed NF, and was transferred to the authors' burn unit. The wound was treated initially with wide debridement and with a brief delay before finally closing the wound. A collagen matrix such as Integra® Dermal Regeneration Template (Integra LifeSciences, Plainsboro, NJ) in combination with STSG and negative pressure wound treatment, can provide fast recovery resulting in pliable, functional skin..

  • 227.
    Dantonello, Tobias M
    et al.
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Lochbühler, Helmut
    Department of Pediatric Surgery, Olgahospital, Klinikum Stuttgart, Germany.
    Schuck, Andreas
    Department of Radiotherapy, University of Muenster, Münster, Germany.
    Kube, Stefanie
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Godzinski, Jan
    Department of Pediatric Surgery, University of Wroclaw, Poland.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kosztyla, Daniel
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Veit-Friedrich, Iris
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Hallmen, Erika
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Feuchtgruber, Simone
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Wessalowski, Ruediger
    Department of Pediatric Oncology, University of Duesseldorf, Germany.
    Franke, Markus
    Department of Pediatric Surgery, University of Freiburg, Germany.
    Bielack, Stefan S
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Klingebiel, Thomas
    Department of Pediatric Oncology, University of Frankfurt, Germany.
    Koscielniak, Ewa
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 11, p. 3579-3586Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.

    METHODS:

    We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.

    RESULTS:

    One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.

    CONCLUSIONS:

    Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.

  • 228. Darkahi, Bahman
    et al.
    Sandblom, Gabriel
    Liljeholm, Hakan
    Videhult, Per
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Rasmussen, Ib Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Biliary Microflora in Patients Undergoing Cholecystectomy2014In: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 15, no 3, p. 262-265Article in journal (Refereed)
    Abstract [en]

    Background: The management of acute cholecystitis requires a sound knowledge of the biliary microflora. Methods: Bile samples were taken for culture according to a standard routine during all cholecystectomies performed from April 2007 to February 2009 in the Department of Surgery at Enkoping Hospital. The use of antibiotics within the 3-mo period before surgery, indication for surgery, prophylactic antibiotics, and post-operative complications were recorded prospectively. Results: Altogether, 246 procedures were performed during the study period, of which 149 (62%) were done on women. The mean (SD) age of the study subjects was 49 +/- 16y. Bacterial growth was seen in cultures from 34 (14%) of the subjects. The mean age of subjects with positive cultures was 64y and that of subjects with negative cultures was 47y (p<0.001). Positive culture was seen in 16 (31%) of the 51 patients who underwent operations for acute cholecystitis, whereas positive cultures were obtained in 18 of 195 patients without acute cholecystitis (9%) (p<0.001). Resistance to ampicillin was recorded in three of 34 (9%) of the cultures with bacterial growth, to co-trimoxazole in one of the 34 (3%) cultures, to fluoroquinolones in one of the 34 (3%) cultures, and to cephalosporins in one of the 34 (3%) cultures. Resistance to piperacillin-tazobactam was not observed in any of the cultures. In multivariable logistic regression analysis, a positive culture was the only factor significantly associated with risk for post-operative infectious complications (p<0.05). Discussion: Bacterial growth in the bile is observed more often in patients undergoing surgery for acute cholecystitis. The microflora of the bile is probably important for the outcome of surgery, but further studies are required for assessing the effectiveness of measures for preventing infectious post-operative complications.

  • 229. Daryapeyma, Alireza
    et al.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wahlgren, Carl-M
    Healthcare-associated Infections After Lower Extremity Revascularization2014In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 48, no 1, p. 72-77Article in journal (Refereed)
    Abstract [en]

    Objective: This population-based study aims to elucidate the incidence of healthcare-associated infections (HCAI) and related risk factors in non-emergent, open and endovascular lower extremity vascular procedures. Method: This was a retrospective analysis of prospectively collected data from the Swedish National Vascular Surgery registry (Swedvasc), National Patient registry, and Cause of Death registry. A nationwide survey of all postoperative infections among patients who have undergone non-emergent open and endovascular surgery for lower extremity arterial disease between January 2005 to December 2010 (n = 10,547) has been performed. Data were retrieved from the National Vascular Surgery registry and cross-matched with the National Patient and Cause of Death registries. The primary purpose of the study was to identify the rate of 30-day postoperative infections and the associated risk factors for the different classes of lower extremity ischemia and operative procedures. Results: The study cohort included patients with claudication 27.0% (n =- 2,827) and critical limb ischemia (CLI), consisting of rest pain 17.0% (n = 1,835) and ulceration/gangrene 56.0% (n = 5,885) undergoing endovascular intervention (n = 6,262; 59.0%), thromboendarterectomy (n = 1,061; 10.0%), or bypass surgery (n = 3,224; 31.0%). The total incidence of postoperative infection (<30-days) was 9.7% (n = 1,019), including skin and soft tissue infection (n = 735; 6.9%), urinary tract infection (n = 168; 1.6%), pneumonia (n = 114; 1.1%), and sepsis (n = 91; 0.9%). In claudicants, the risk of infection was increased eightfold for bypass surgery compared with endovascular intervention (odds ratio 8.4, 95% confidence interval 5.0-14). Risk factors associated with infection were degree of lower extremity ischemia, diabetes, renal insufficiency, and heart and lung disease (p < .05). Conclusion: The postoperative rate of HCAI is associated with cardiovascular risk factors, operative method, and degree of lower extremity ischemia. This may be of assistance when deciding on the type of operative procedure for these patients. 

  • 230.
    Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The Use of Pre- or Postoperative Antibiotics in Surgery for Appendicitis: A Systematic Review2014In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 103, no 1, p. 14-20Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: The aim of this study was to review the literature regarding the use of pre- and/or postoperative antibiotics in the management of appendicitis, using data obtained from PubMed and the Cochrane Library.

    MATERIAL AND METHODS: A literature search was conducted using the terms "appendicitis" combined with "antibiotics." Studies were selected based on relevance for the evidence on prophylactic and postoperative treatment with regard to the route and duration of drug administration and the findings of surgery.

    RESULTS: Patients with acute appendicitis should receive preoperative, broad-spectrum antibiotics. The use of postoperative antibiotics is only recommended in cases of perforation, and treatment should then be given intravenously, for a minimum period of 3-5 days for adult patients, until clinical signs such as fever resolve and laboratory parameters such as C-reactive protein curve and white blood cell (WBC) start to decline.

    CONCLUSION: Preoperative antibiotic prophylaxis is recommended in all patients with acute appendicitis, whereas postoperative antibiotics only in cases of perforation.

  • 231.
    Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kaltsas, Gregory
    Univ Athens, Laiko Hosp, Dept Propauped Internal Med 1, Endocrine Oncol Unit, Athens, Greece.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Tsolakis, Apostolos V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology. Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden; Karolinska Univ Hosp, Canc Ctr Karolinska, CCK, Stockholm, Sweden.
    Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 107, no 4, p. 355-365Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Lung carcinoids (LCs) are often diagnosed at an early stage and surgical intervention becomes the next phase of treatment. To date, there is lack of long-term follow-up data after surgery and prognostication based on WHO classification criteria and evolving prognostic markers, particularly the expression of somatostatin receptors (SSR).

    Methods: We included 102 consecutive patients (72 women; age at baseline 51 ± 16 years [mean ± SD]) with LCs, who underwent thoracic surgery (n = 99) and/or laser treatment (n = 8). Hospital charts were reviewed for clinico-pathological parameters. Immunohistochemical (IHC) expression of SSR1–5 and other novel markers were studied with regard to their prognostic value.

    Results: Five- and 10-year overall survival (OS) was 96 and 83% respectively; relative survival (RS) was 101 and 93% respectively; and event-free survival (EFS) was 80 and 67% respectively. Independent prognostic factors for OS, RS and/or EFS were age at diagnosis, histopathological type and the presence of ipsilateral mediastinal subcarinal lymph node metastases. Macro-radicality of resective surgery and its extent were associated with increased OS and EFS. The IHC expression of SSR1–5 and other novel markers was not associated with OS or EFS.

    Conclusion: The long-term outcome of surgically treated patients with LCs is favourable. Age, histopathological type and ipsilateral mediastinal subcarinal lymph node status at baseline were independent prognostic factors for survival and disease recurrence or progression. The extent of surgery and operative macro-radicality also had an impact on prognosis. None of the IHC markers tested appeared to be associated with disease prognosis.

  • 232.
    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.

     

  • 233.
    Daskalakis, Kosmas
    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.
    Karakatsanis, Andreas
    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.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ex vivo activity of cytotoxic drugs and targeted agents in Small Intestinal NETsManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Small Intestinal Neuroendocrine Tumours (SI-NET) are considered to be generally resistant to systemic treatment. To date predictive markers for drug activity are lacking.

    Patients and Methods: Tumour samples from 27 patients with SI-NET were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinico-pathological variables and pre-treatment biomarkers.

    Results: For standard cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinums, gemcitabine and doxorubicin compared with CRC. For targeted kinase inhibitors, SI-NET was among the most sensitive diagnoses. CLL and ovarian cancer were generally the most sensitive diagnoses to both cytotoxic drugs and protein kinase inhibitors. The mTOR inhibitor sirolimus exhibited modest cytotoxic activity.

    Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors.

    Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo.

    Conclusions: SI-NETs exhibit variable but generally intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinico-pathological factors and currently used biomarkers were not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NETs. The great variability in drug sensitivity calls for individualized selection of therapy.

  • 234.
    Daskalakis, Kosmas
    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.
    Karakatsanis, Andreas
    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.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors2018In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 25, no 4, p. 471-480Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinum, gemcitabine and doxorubicin compared with CRC. For several of the targeted kinase inhibitors, SI-NET was among the most sensitive solid tumor types. CLL and ovarian cancer were generally the most sensitive tumor types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors. Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinicopathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy.

  • 235. Dasmah, Amir
    et al.
    Kashani, Hossein
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Rasmusson, Lars
    Integration of fluoridated implants in onlay autogenous bone grafts: An experimental study in the rabbit tibia2014In: Journal of Cranio-Maxillofacial Surgery, ISSN 1010-5182, E-ISSN 1878-4119, Vol. 42, no 6, p. 796-800Article in journal (Refereed)
    Abstract [en]

    Introduction: Bone augmentation before treatment with endosseous implants is a common procedure for rehabilitation of the edentulous jaw. Both machined and surface modified implants have been used in one-stage and two-stage surgery protocols with varying results and survival rates. The influence of surface modification on the integration of implants has been documented in both non-grafted and grafted bone. The aim of this study was to compare the integration and stability of surface modified fluoridated vs. machined implants when placed simultaneously with an onlay bone graft. Material and methods: Eight rabbits were used in this study. A disc shaped bone graft was harvested from each side of the sagittal suture of the calvarial bone and fixed bi-cortically to the proximal tibial metaphysis by means of a dental implant, 9 mm long and 3.5 mm in diameter with a smooth machined surface as control and a blasted, fluoridated surface as test. Test and control sides were randomised. After a healing time of 8 weeks, the rabbits were sacrificed and the implants were removed en block for light microscopic analysis. Bone to implant contact (BIC) was registered as well as the amount of bone filling a rectangle indicating a region of interest (ROI) in the grafted area. Resonance frequency analysis (RFA) was conducted both at the time of surgery and at the end of the study. Results: Our results showed statistically significant differences in BIC within the grafted area and the total bone to implant contact between the test and control sides in favour of the surface modified implants. The bone area filling the threads within a region of interest showed no statistically significant difference between the test and control sides. RFA showed higher implant stability with significant differences at the time of sacrifice in favour of the fluoridated implants. Conclusion: Surface modified fluoridated implants showed a higher degree of osseointegration and stability in onlay bone grafts compared with control implants with machined surface texture.  

  • 236.
    de Boniface, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Capio St Gorans Hosp, Breast Ctr, Dept Surg, Sankt Goransplan 1, SE-11281 Stockholm, Sweden.
    Frisell, J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 12, p. 1607-1614Article in journal (Refereed)
    Abstract [en]

    Background: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking.

    Methods: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy.

    Results: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79.5 versus 64.3 per cent respectively at 13 years; P < 0.001) and breast cancer-specific survival (90.5 versus 84.0 per cent at 13 years; P < 0.001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98.3 versus 96.2 per cent; P < 0.001).

    Conclusion: The present data support the superiority or BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

  • 237.
    De Waele, J. J.
    et al.
    Ghent Univ Hosp, Dept Crit Care Med, De Pintelaan 185, B-9000 Ghent, Belgium..
    Kimball, E.
    Univ Utah, Dept Surg, Hlth Sci Ctr, Salt Lake City, UT USA..
    Malbrain, M.
    Ziekenhuis Netwerk Antwerpen Stuivenberg, Intens Care Unit, Antwerp, Belgium.;Ziekenhuis Netwerk Antwerpen Stuivenberg, High Care Burn Unit, Antwerp, Belgium..
    Nesbitt, I.
    Freeman Rd Hosp, Anaesthesia & Crit Care, Newcastle Upon Tyne, Tyne & Wear, England..
    Cohen, J.
    Rabin Med Ctr, Gen Intens Care Unit, Petah Tiqwa, Israel.;Tel Aviv Univ, Sackler Sch Med, Crit Care & Anaesthesia, IL-69978 Tel Aviv, Israel..
    Kaloiani, V.
    Tbilisi State Med Univ, Cent Clin, Dept Anaesthesiol Emergency Med & Crit Care, Tbilisi, Rep of Georgia..
    Ivatury, R.
    Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA..
    Mone, M.
    Univ Utah, Dept Surg, Hlth Sci Ctr, Salt Lake City, UT USA..
    Debergh, D.
    Ghent Univ Hosp, Dept Crit Care Med, De Pintelaan 185, B-9000 Ghent, Belgium.;Artevelde Univ Coll, Ghent, Belgium..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Decompressive laparotomy for abdominal compartment syndrome2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 6, p. 709-715Article in journal (Refereed)
    Abstract [en]

    Background: The effect of decompressive laparotomy on outcomes in patients with abdominal compartment syndrome has been poorly investigated. The aim of this prospective cohort study was to describe the effect of decompressive laparotomy for abdominal compartment syndrome on organ function and outcomes. Methods: This was a prospective cohort study in adult patients who underwent decompressive laparotomy for abdominal compartment syndrome. The primary endpoints were 28-day and 1-year all-cause mortality. Changes in intra-abdominal pressure (IAP) and organ function, and laparotomy-related morbidity were secondary endpoints. Results: Thirty-three patients were included in the study (20 men). Twenty-seven patients were surgical admissions treated for abdominal conditions. The median (i.q.r.) Acute Physiology And Chronic Health Evaluation (APACHE) II score was 26 (20-32). Median IAP was 23 (21-27) mmHg before decompressive laparotomy, decreasing to 12 (9-15), 13 (8-17), 12 (9-15) and 12 (9-14) mmHg after 2, 6, 24 and 72 h. Decompressive laparotomy significantly improved oxygenation and urinary output. Survivors showed improvement in organ function scores, but non-survivors did not. Fourteen complications related to the procedure developed in eight of the 33 patients. The abdomen could be closed primarily in 18 patients. The overall 28-day mortality rate was 36 per cent (12 of 33), which increased to 55 per cent (18 patients) at 1 year. Non-survivors were no different from survivors, except that they tended to be older and on mechanical ventilation. Conclusion: Decompressive laparotomy reduced IAP and had an immediate effect on organ function. It should be considered in patients with abdominal compartment syndrome.

  • 238. Dehghani, F.
    et al.
    Sayan, M.
    Conrad, A.
    Evers, J.
    Ghadban, C.
    Blaheta, R.
    Korf, H. -W
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Inhibition of microglial and astrocytic inflammatory responses by the immunosuppressant mycophenolate mofetil2010In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 36, no 7, p. 598-611Article in journal (Refereed)
    Abstract [en]

    Aims: Nucleotide depletion induced by the immunosuppressant mycophenolate mofetil (MMF) has been shown to exert neuroprotective effects. It remains unclear whether nucleotide depletion directly counteracts neuronal demise or whether it inhibits microglial or astrocytic activation, thereby resulting in indirect neuroprotection. Methods: Effects of MMF on isolated microglial cells, astrocyte/microglial cell co-cultures and isolated hippocampal neurones were analysed by immunocytochemistry, quantitative morphometry, and elisa. Results: We found that: (i) MMF suppressed lipopolysaccharide-induced microglial secretion of interleukin-1 beta, tumour necrosis factor-alpha and nitric oxide; (ii) MMF suppressed lipopolysaccharide-induced astrocytic production of tumour necrosis factor-alpha but not of nitric oxide; (iii) MMF strongly inhibited proliferation of both microglial cells and astrocytes; (iv) MMF did not protect isolated hippocampal neurones from excitotoxic injury; and (v) effects of MMF on glial cells were reversed after treatment with guanosine. Conclusions: Nucleotide depletion induced by MMF inhibits microglial and astrocytic activation. Microglial and astrocytic proliferation is suppressed by MMF-induced inhibition of the salvage pathway enzyme inosine monophosphate dehydrogenase. The previously observed neuroprotection after MMF treatment seems to be indirectly mediated, making this compound an interesting immunosuppressant in the treatment of acute central nervous system lesions.

  • 239.
    Deijen, Charlotte L.
    et al.
    Vrije Univ Amsterdam.
    Vasmel, Jeanine E.
    Vrije Univ Amsterdam.
    de Lange-de Klerk, Elly S. M.
    Vrije Univ Amsterdam.
    Cuesta, Miguel A.
    Vrije Univ Amsterdam.
    Coene, Peter-Paul L. O.
    Maasstad Hosp, Rotterdam, Netherlands..
    Lange, Johan F.
    Erasmus MC, Rotterdam, Netherlands..
    Meijerink, W. J. H. Jeroen
    Vrije Univ Amsterdam.
    Jakimowicz, Jack J.
    Delft Univ Technol.
    Jeekel, Johannes
    Erasmus MC, Dept Surg, Rotterdam.
    Kazemier, Geert
    Vrije Univ Amsterdam.
    Janssen, Ignace M. C.
    Rijnstate Hosp, Dept Surg, Arnhem.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Haglind, Eva
    Sahlgrens Univ Hosp.
    Bonjer, H. Jaap
    Vrije Univ Amsterdam.
    Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer2017In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 31, no 6, p. 2607-2615Article in journal (Refereed)
    Abstract [en]

    Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

  • 240.
    Delgado, Anna Falk
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden; Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
    Falk Delgado, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET: a bivariate diagnostic test accuracy meta-analysis2018In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 91, no 1082, article id 20170426Article, review/survey (Refereed)
    Abstract [en]

    Objective: To perform a meta-analysis evaluating the diagnostic accuracy of 11C-methionine (MET) positron emission tomography (PET) to discriminate between primary low-grade glioma (LGG) and high-grade glioma (HGG).

    Methods: A systematic database search was performed by a librarian in relevant databases with the latest search on 07 November 2016. Hits were assessed for inclusion independently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient data were analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity. This study is registered with PROSPERO, number CRD42016050747.

    Results: Out of 1828 hits, 13 studies comprising of 241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI) (0.66–0.88) and a summary false positive rate of 0.28, 95% CI (0.19–0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21.

    Conclusion: MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG.

    Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.

  • 241.
    Delgado Verdugo, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Genetic Aspects of Endocrine Tumorigenesis: A Hunt for the Endocrine Neoplasia Gene2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Endocrine tumors arise from endocrine glands. Most endocrine tumors are benign but malignant variants exist. Several endocrine neoplasms display loss of parts of chromosome 11 or 18, produce hormones and responds poorly to conventional chemotherapeutics. The multiple endocrine neoplasia syndromes are mainly confined to endocrine tumors. This opens the question if there exists a single or several endocrine tumor genes.

    The aim of the study was to describe genetic derangements in endocrine tumors.

    Paper I: Investigation of mutational status of SDHAF2 in parathyroid tumors. SDHAF2 is located in the proximity of 11q13, a region that frequently displays loss in parathyroid tumors. We established that mutations in SDHAF2 are infrequent in parathyroid tumors.

    Paper II: Study of SDHAF2 gene expression in a cohort of benign pheochromocytomas (PCC) (n=40) and malignant PCC (n=10). We discovered a subset of  benign PCC (28/40) and all malignant PCC (10/10) with significantly lower SDHAF2 expression. Benign PCC with low SDHAF2 expression and malignant tumors consistently expressing low levels of SDHAF2 were methylated in the promoter region. SDHAF2 expression was restored in vitro after treatment with 5- aza-2-deoxycytidine.

    Paper III: HumanMethylation27 array (Illumina) covering 27578 CpG sites spanning over 14495 genes were analyzed in a discovery cohort of 10 primary small neuroendocrine tumors (SI-NETs) with matched metastases. 2697 genes showed different methylation pattern between the primary tumor and its metastasis. We identified several hypermethylated genes in key regions. Unsupervised clustering of the tumors identified three distinct clusters, one with a highly malignant behavior.

    Paper IV: Loss of chromosome 18 is the most frequent genetic aberration in SI-NETs. DNA from SI-NETs were subjected to whole exome capture sequencing and high resolution SNP array. Genomic profiling revealed loss of chromosome 18 in 5 out of 7 SI-NETs. No tumor-specific somatic mutation on chromosome 18 was identified which suggests involvement of other mechanisms than point mutations in SI-NET tumorigenesis.

    Paper V: The cost for diagnostic genetic screening of common susceptibility genes in PCC is expensive and labor intensive. Three PCC from three patients with no known family history were chosen for exome capture sequencing. We identified three variants in known candidate genes. We suggest that exome-capture sequencing is a quick and cost-effective tool.

    List of papers
    1. Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism
    Open this publication in new window or tab >>Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism
    Show others...
    2010 (English)In: Endocrine, ISSN 0969-711X, Vol. 38, no 3, p. 397-401Article in journal (Refereed) Published
    Abstract [en]

    To investigate the SDHAF2 gene and its effect on primary hyperparathyroidism. Parathyroid tumors causing primary hyperparathyroidism (pHPT) are one of the more common endocrine neoplasias. Loss of heterozygosity at chromosome 11q13 is the most common chromosomal aberration in parathyroid tumors occurring in about 40% of sporadic tumors. Only 15-19% display somatic mutations in the MEN1 gene, which suggest that this chromosomal region may harbor additional genes of importance in parathyroid tumor development. The SDHAF2 (formerly SDH5) gene is a recently identified neuroendocrine tumor suppressor gene at this locus, and inherited mutations of the SDHAF2 gene has been linked to familial paraganglioma. We demonstrate that the SDHAF2 gene is expressed in parathyroid tissue using RT-PCR. Because detection of inactivating mutations is the major criterion for validating a candidate tumor suppressor, we used automated sequencing of the coding region and intron/exon boundaries in 80 sporadic parathyroid adenomas from patients with pHPT. A known polymorphisms (A to G substitution; rs879647) was identified in 9/80 parathyroid tumors but no tumor-specific somatic mutational aberrations, such as nonsense, frameshift, or other inactivating mutations were identified. The SDHAF2 gene is expressed in parathyroid tissue. However, somatic mutations of the SDHAF2 tumor suppressor gene are unlikely to frequently contribute to parathyroid tumor development in sporadic pHPT.

    Keywords
    Hyperparathyroidism, Parathyroid, Paraganglioma, Succinate dehydrogenase, SDHAF2
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-139273 (URN)10.1007/s12020-010-9399-0 (DOI)000284116000010 ()
    Available from: 2010-12-22 Created: 2010-12-22 Last updated: 2016-12-20Bibliographically approved
    2. Epigenetic inactivation of SDHAF2 is a frequent event in benign and malignant pheochromocytomas.
    Open this publication in new window or tab >>Epigenetic inactivation of SDHAF2 is a frequent event in benign and malignant pheochromocytomas.
    (English)Manuscript (preprint) (Other academic)
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:uu:diva-224109 (URN)
    Available from: 2014-05-04 Created: 2014-05-04 Last updated: 2018-01-11
    3. Global DNA methylation patterns in small intestinal neuroendocrine tumors (SI-NETs)
    Open this publication in new window or tab >>Global DNA methylation patterns in small intestinal neuroendocrine tumors (SI-NETs)
    Show others...
    2014 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 1, p. L5-L7Article in journal (Refereed) Published
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are rare hormone producing tumors and are often diagnosed at advanced stage. The genetic and epigenetic background of SI-NETs are poorly understood, but several reports have indicated chromosomal losses at 18.21-qter and 11q22-q23. The aim of this study was to characterize CpG DNA methylation status of primary SI-NETs and the corresponding lymph node metastases. We used the commercially available HumanMethylation27 Beadchip array (Illumina), which covers 27578 CpG sites spanning over 14495 genes, and analyzed a discovery cohort of 10 primary SI-NETs with matched metastases. Messenger- mRNA, were determined for selected genes in a 47 tumors. In comparison to the primary tumors, the metastases showed 2697 statistically significant differentially genes. Metastases were generally less methylated than primary tumors. The relative mRNA expression level of the differentially methylated genes AXL, CRMP1, FGF5, and APOBEC3C largely reflected the methylation status. MAPK4, RUNX3, TP73, CCND1, CHFR, AHRR, and Rb1 known to be hypermethylated in other cancer types, displayed overall high methylation level (β-value ≥ 0.9). Methylation (β -value >0,7) at 18q21-qter and 11q22-q23 were detected in genes SETBP1, ELAC1, MBD1, MAPK4, TCEB3C and ARVC1, MMP8, BTG4, APOA1, FAM89B, HSPB1, respectively. Furthermore unsupervised clustering of the tumors identified three distinct clusters, one with a highly malignant behavior. Our data supports involvement of CpG DNA methylation in metastatic progression of SI-NETs and this could present a possibility to identify more aggressive tumors based on DNA methylation.

    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-212142 (URN)10.1530/ERC-13-0481 (DOI)000334279600002 ()24192231 (PubMedID)
    Available from: 2013-12-06 Created: 2013-12-06 Last updated: 2019-10-30
    4. Exome Sequencing reveal no recurrent mutations on chromosome 18 in small intestinal neuroendocrine tumors; Ruling out a suspect?
    Open this publication in new window or tab >>Exome Sequencing reveal no recurrent mutations on chromosome 18 in small intestinal neuroendocrine tumors; Ruling out a suspect?
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-224110 (URN)
    Available from: 2014-05-04 Created: 2014-05-04 Last updated: 2018-01-11
    5. Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma
    Open this publication in new window or tab >>Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma
    Show others...
    2013 (English)In: Endocrine connections, ISSN 2049-3614, Vol. 2, no 2, p. 104-111Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of genes is constantly growing and the 11 genes together consist of 144 exons. A genetic screening test is extensively time consuming and expensive. Hence, we introduce next-generation sequencing (NGS) as a time-efficient and cost-effective alternative.

    METHODS:

    Tumour lesions from three patients with apparently sporadic PCC were subjected to whole exome sequencing utilizing Agilent Sureselect target enrichment system and Illumina Hi seq platform. Bioinformatics analysis was performed in-house using commercially available software. Variants in PCC and PGL susceptibility genes were identified.

    RESULTS:

    We have identified 16 unique genetic variants in PCC susceptibility loci in three different PCC, spending less than a 30-min hands-on, in-house time. Two patients had one unique variant each that was classified as probably and possibly pathogenic: NF1 Arg304Ter and RET Tyr791Phe. The RET variant was verified by Sanger sequencing.

    CONCLUSIONS:

    NGS can serve as a fast and cost-effective method in the clinical genetic screening of PCC. The bioinformatics analysis may be performed without expert skills. We identified process optimization, characterization of unknown variants and determination of additive effects of multiple variants as key issues to be addressed by future studies.

    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-212875 (URN)10.1530/EC-13-0009 (DOI)23781326 (PubMedID)
    Available from: 2013-12-16 Created: 2013-12-16 Last updated: 2019-10-30Bibliographically approved
  • 242.
    Delgado Verdugo, Alberto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Starker, Lee F
    Stålberg, Peter
    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.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Global DNA methylation patterns in small intestinal neuroendocrine tumors (SI-NETs)2014In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 1, p. L5-L7Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are rare hormone producing tumors and are often diagnosed at advanced stage. The genetic and epigenetic background of SI-NETs are poorly understood, but several reports have indicated chromosomal losses at 18.21-qter and 11q22-q23. The aim of this study was to characterize CpG DNA methylation status of primary SI-NETs and the corresponding lymph node metastases. We used the commercially available HumanMethylation27 Beadchip array (Illumina), which covers 27578 CpG sites spanning over 14495 genes, and analyzed a discovery cohort of 10 primary SI-NETs with matched metastases. Messenger- mRNA, were determined for selected genes in a 47 tumors. In comparison to the primary tumors, the metastases showed 2697 statistically significant differentially genes. Metastases were generally less methylated than primary tumors. The relative mRNA expression level of the differentially methylated genes AXL, CRMP1, FGF5, and APOBEC3C largely reflected the methylation status. MAPK4, RUNX3, TP73, CCND1, CHFR, AHRR, and Rb1 known to be hypermethylated in other cancer types, displayed overall high methylation level (β-value ≥ 0.9). Methylation (β -value >0,7) at 18q21-qter and 11q22-q23 were detected in genes SETBP1, ELAC1, MBD1, MAPK4, TCEB3C and ARVC1, MMP8, BTG4, APOA1, FAM89B, HSPB1, respectively. Furthermore unsupervised clustering of the tumors identified three distinct clusters, one with a highly malignant behavior. Our data supports involvement of CpG DNA methylation in metastatic progression of SI-NETs and this could present a possibility to identify more aggressive tumors based on DNA methylation.

  • 243.
    Dellagrammaticas, Demos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Baderkhan, Hassan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Management of Aortic Sac Enlargement Following Successful EVAR in a Frail Patient2016In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 51, no 2, p. 302-308Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An enlarging aneurysm after endovascular aneurysm repair (EVAR) without clear endoleak is a clinical challenge. Management of this problem is guided by the current evidence for adequate EVAR follow up and recommended thresholds for re-intervention. In a frail patient, careful risk assessment of aneurysm related mortality against the risks associated with examinations and interventions is required.

    METHODS: The literature was reviewed for imaging modalities for EVAR follow up and their advantages and disadvantages. The current evidence and guideline recommendations regarding follow up and re-intervention after EVAR were assessed in relation to the presented case.

    RESULTS: To detect sac expansion after EVAR, repeated examinations with the same imaging modality are needed. Verified expansion must be above the inter-observer variation of the method used. Although duplex ultrasound is an excellent modality for EVAR follow up, the finding of a significant expansion on duplex requires further examination, primarily with computed tomography angiography to assess sealing, stent graft integrity, and presence of endoleak. A frail patient should be assessed thoroughly before any kind of surgical intervention, the extent of which is related to the identified or suspected cause of expansion.

    CONCLUSION: Failure to totally exclude the aneurysm from continuing circulation, pressure and endoleak remains a potential shortcoming of EVAR. Significant sac expansion is an indication of EVAR failure. Decisions regarding further examinations or intervention are guided by the stability of the initial EVAR performed, the cause and extent of expansion, and the patient's comorbidities.

  • 244. DeLuca, S.
    et al.
    Sitara, D.
    Kang, K.
    Marsell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jonsson, Kenneth B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Taguchi, T.
    Erben, R. G.
    Razzaque, M. S.
    Lanske, Beate
    Amelioration of the premature ageing-like features of Fgf-23 knockout mice by genetically restoring the systemic actions of FGF-232008In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 216, no 3, p. 345-355Article in journal (Refereed)
    Abstract [en]

    Genetic ablation of fibroblast growth factor 23 from mice (Fgf-23−/−) results in a short lifespan with numerous abnormal biochemical and morphological features. Such features include kyphosis, hypogonadism and associated infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue calcifications, and generalized atrophy of various tissues. To determine whether these widespread anomalies in Fgf-23−/− mice can be ameliorated by genetically restoring the systemic actions of FGF-23, we generated Fgf-23−/− mice expressing the human FGF-23 transgene in osteoblasts under the control of the 2.3 kb α1(I) collagen promoter (Fgf-23−/−/hFGF-23-Tg double mutants). This novel mouse model is completely void of all endogenous Fgf-23 activity, but produces human FGF-23 in bone cells that is subsequently released into the circulation. Our results suggest that lack of Fgf-23 activities results in extensive premature ageing-like features and early mortality of Fgf-23−/− mice, while restoring the systemic effects of FGF-23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants. With regard to their serum biochemistry, double mutants reversed the severe hyperphosphataemia, hypercalcaemia, and hypervitaminosis D found in Fgf-23−/− littermates; rather, double mutants show hypophosphataemia and normal serum 1,25-dihydroxyvitamin D3 levels similar to pure FGF-23 Tg mice. These changes were associated with reduced renal expression of NaPi2a and 1α-hydroxylase, compared to Fgf-23−/− mice. FGF-23 acts to prevent widespread abnormal features by acting systemically to regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model provides us with an in vivo tool to study the systemic effects of FGF-23 in regulating mineral ion metabolism and preventing multiple abnormal phenotypes without the interference of native Fgf-23.

  • 245. Derogar, M.
    et al.
    Blomberg, J.
    Sadr-Azodi, O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Hospital teaching status and volume related to mortality after pancreatic cancer surgery in a national cohort2015In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 102, no 5, p. 548-557Article in journal (Refereed)
    Abstract [en]

    Background: The association between hospital teaching status and mortality after pancreatic resection is not well explored. Although hospital volume is related to short-term mortality, the effect on long-term survival needs investigation, taking into account hospital teaching status and selective referral patterns. Methods: This was a nationwide retrospective register-based cohort study of patients undergoing pancreatic resection between 1990 and 2010. Follow-up for survival was carried out until 31 December 2011. The associations between hospital teaching status and annual hospital volume and short-, intermediate- and long-term mortality were determined by use of multivariable Cox regression models, which provided hazard ratios (HRs) with 95 per cent c.i. The analyses were mutually adjusted for hospital teaching status and volume, as well as for patients' sex, age, education, co-morbidity, type of resection, tumour site and histology, time interval, referral and hospital clustering. Results: A total of 3298 patients were identified during the study interval. Hospital teaching status was associated with a decrease in overall mortality during the latest interval (years 2005-2010) (university versus non-university hospitals: HR 0.72, 95 per cent c.i. 0.56 to 0.91; P = 0.007). During all time periods, hospital teaching status was associated with decreased mortality more than 2 years after surgery (university versus non-university hospitals: HR 0.86, 0.75 to 0.98; P = 0.026). Lower annual hospital volume increased the risk of short-term mortality (HR for 3 or fewer compared with 4-6 pancreatic cancer resections annually: 1.60, 1.04 to 2.48; P = 0.034), but not long-term mortality. Sensitivity analyses with adjustment for tumour stage did not change the results. Conclusion: Hospital teaching status was strongly related to decreased mortality in both the short and long term. This may relate to processes of care rather than volume per se. Very low-volume hospitals had the highest short-term mortality risk.

  • 246.
    Derogar, Maryam
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden..
    Dahlstrand, Hanna
    Karolinska Univ Hosptital, Dept Oncol, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Carlsson, Stefan
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Bjartell, Anders
    Lund Univ, Skane Univ Hosp, Dept Urol, Lund, Sweden..
    Hugosson, Jonas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Axen, Elin
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lagerkvist, Mikael
    UroClin, Stockholm, Sweden..
    Nyberg, Tommy
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Stranne, Johan
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Thorsteinsdottir, Thordis
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Univ Iceland, Sch Hlth Sci, Fac Nursing, Reykjavik, Iceland..
    Wallerstedt, Anna
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Haglind, Eva
    Univ Gothenburg, Sahlgrenska Acad, SSORG, Dept Surg,Inst Clin Sci, Gothenburg, Sweden..
    Wiklund, Peter
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Steineck, Gunnar
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Div Clin Canc Epidemiol,Dept Oncol, Box 100, S-40530 Gothenburg, Sweden.;Karolinska Inst, Dept Oncol Pathol, Div Clin Canc Epidemiol, Stockholm, Sweden..
    Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 12, p. 1467-1476Article in journal (Refereed)
    Abstract [en]

    Background: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery. Material and methods: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression. Results: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55). Conclusion: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.

  • 247.
    Dimberg, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Janiec, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Re-exploration for bleeding associated with increased incidence of the need for reintervention after coronary artery bypass graft surgery2019In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 28, no 2, p. 214-221Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Re-exploration for bleeding after cardiac surgery increases the risk of other severe postoperative complications and early mortality. Patients re-explored for bleeding after coronary artery bypass grafting are potentially subject to threats to graft patency. Our goal was to assess the effects of re-exploration for bleeding regarding the incidence of coronary angiographies, the need for coronary reintervention and mortality during long-term follow-up.

    METHODS: Within the SWEDEHEART registry, all isolated coronary artery bypass operations with a single internal mammary artery and saphenous vein graft in patients aged 40-80 between the years 2005 and 2015 were identified. Incidences of coronary angiography and the subsequent need for coronary reintervention were recorded, and multivariable adjusted hazard ratios (HRs) were calculated.

    RESULTS: The study cohort consisted of 27 957 patients, and the mean follow-up time was 6.5 ± 3.1 years. The incidence of re-exploration for bleeding was 3.8% (n = 1071). The cumulative incidence [95% confidence interval (CI)] of a clinically occurring coronary angiography within 1 year after surgery was 7.8% (6.3-9.7) in re-explored and 4.8% (4.6-5.1) in non-re-explored patients, and the adjusted HR was 1.64 (1.31-2.06), (P < 0.001). The cumulative incidence of the need for coronary reintervention within 1 year (95% CI) was 4.9% (3.7-6.4) in re-explored and 2.6% (2.4-2.8) in non-re-explored patients, and the adjusted HR was 1.91 (1.43-2.56). No difference in incidence or hazard ratio was observed beyond the first year. Mortality rate was increased within but not beyond 90 days after surgery.

    CONCLUSIONS: Re-exploration for bleeding is associated with an increased risk for the need of repeat coronary reintervention during the first year after coronary artery bypass surgery.

  • 248.
    Djavani Gidlund, Khatereh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Intra-abdominal Hypertension and Colonic Hypoperfusion after Abdominal Aortic Aneurysm Repair2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colonic ischaemia (CI), Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are devastating complications after abdominal aortic aneurysm (AAA) surgery. The aims of this thesis were to study the incidence and clinical consequences of IAH/ACS and the association between CI and intra-abdominal pressure (IAP) among patients undergoing OR for ruptured AAA (rAAA), to compare extraluminal pHi monitoring, with standard intra-luminal monitoring among patients operated on for AAA, and to study the frequency and clinical consequences of IAH/ACS after endovascular repair (EVAR) for rAAA.

    The incidence of ACS was 26% in a retrospective study of 27 patients undergoing OR for rAAA. Consensus definitions on IAH/ACS were appropriate for patients after OR for rAAA: 78% (7/9) of patients with IAH grade III or IV developed organ failure and all patients who developed CI had some degree of IAH. Active fluid resuscitation treating hypovolaemia to avoid CI may partly cause IAH. The association between CI and IAP was investigated in a prospective study on 29 patients operated on for rAAA, 86% (25/29) were treated for hypovolaemia and ten (34%) had both IAH and CI. Since monitoring colonic perfusion is very important and there is no ideal method, a new technique, extraluminal colonic tonometry to detect colonic perfusion was compared with standard intraluminal tonometry. Although, this new method was not able to determine the severity of ischaemia it may serve as a screening test. EVAR of rAAA is feasible and patients may benefit from this less invasive procedure. Of 29 patients treated with this technique, 10% developed ACS, and all patients except one with preoperative shock developed some degree of IAH.

    In conclusion, IAP/ACS is common after both OR and EVAR for rAAA, and is associated with adverse outcome. Monitoring IAP and colonic perfusion with timely intervention may improve outcome.

    List of papers
    1. Intra-abdominal hypertension and abdominal compartment syndrome following surgery for ruptured abdominal aortic aneurysm.
    Open this publication in new window or tab >>Intra-abdominal hypertension and abdominal compartment syndrome following surgery for ruptured abdominal aortic aneurysm.
    2006 (English)In: Eur J Vasc Endovasc Surg, ISSN 1078-5884, Vol. 31, no 6, p. 581-4Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To investigate the importance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS), based on the December 2004 consensus definition, on outcome after surgery for ruptured abdominal aortic aneurysm (rAAA). METHODS: Twenty-seven patients underwent open surgery for rAAA after the introduction of intra-abdominal pressure (IAP) measurements among patients at risk of IAH. Case-records were reviewed retrospectively. Seventeen patients underwent IAP-monitoring. RESULTS: Of eight patients with IAP <21 mmHg none developed colonic ischaemia or ACS. Of four patients with IAP 21-25 mmHg (IAH grade III), two underwent colonic resection. One patient treated with open abdomen died from cardiac arrhythmia. Five patients had IAP >25 mmHg (IAH grade IV). All developed ACS. Two were not decompressed and both developed pulmonary complications, one died. Two underwent colonic resection and one was treated with open abdomen, all three survived. Of 10 patients not monitored for IAP, one died of cardiac complications, but no patient developed signs of colonic ischaemia or ACS. Mortality at 30 days and 1 year was 3/27 (11%). CONCLUSION: IAH and ACS were common among patients undergoing surgery for rAAA. The ACS consensus definition seems appropriate in this clinical context. Monitoring IAP, and timely decompression of patients with IAH might improve outcome after surgery for rAAA.

    Keywords
    Abdomen/blood supply, Aged, Aneurysm; Ruptured/*surgery, Aortic Aneurysm; Abdominal/*surgery, Compartment Syndromes/*etiology, Consensus, Female, Humans, Hypertension/*etiology, Incidence, Male, Pilot Projects, Postoperative Complications, Retrospective Studies, Rupture; Spontaneous
    Identifiers
    urn:nbn:se:uu:diva-24385 (URN)16458547 (PubMedID)
    Available from: 2007-04-16 Created: 2007-04-16 Last updated: 2011-05-05
    2. Colonic ischaemia and intra-abdominal hypertension following open repair of ruptured abdominal aortic aneurysm
    Open this publication in new window or tab >>Colonic ischaemia and intra-abdominal hypertension following open repair of ruptured abdominal aortic aneurysm
    2009 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 96, no 6, p. 621-627Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:: The aim was to investigate the association between colonic ischaemia and intra-abdominal pressure (IAP) after surgery for ruptured abdominal aortic aneurysm (rAAA). METHODS:: Sigmoid colon perfusion was monitored with an intramucosal pH (pHi) tonometer. Patients with a pHi of 7.1 or less were treated for suspected hypovolaemia with intravenous colloids and colonoscopy. IAP was measured every 4 h. Patients with an IAP of 20 mmHg or more had neuromuscular blockade, relaparotomy or both. RESULTS:: A total of 52 consecutive patients had open rAAA repair; 30-day mortality was 27 per cent. Eight patients died shortly after surgery. Fifteen were not monitored for practical reasons; mortality in this group was 33 per cent. IAP and pHi were measured throughout the stay in intensive care in the remaining 29 patients. Monitoring led to volume resuscitation in 25 patients, neuromuscular blockade in 16, colonoscopy in 19 and relaparotomy in two. One patient died in this group. Twenty-three of 29 patients had a pHi of 7.1 or less, of whom 15 had a pHi of 6.9 or less. Sixteen had an IAP of 20 mmHg or more, of whom ten also had a pHi below 6.90. Peak IAP values correlated with the simultaneously measured pHi (r = -0.39, P = 0.003). CONCLUSION:: Raised IAP is an important mechanism behind colonic hypoperfusion after rAAA repair. Monitoring IAP and timely intervention may improve outcome.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103187 (URN)10.1002/bjs.6592 (DOI)000266647500009 ()19384909 (PubMedID)
    Available from: 2009-05-15 Created: 2009-05-15 Last updated: 2017-12-13Bibliographically approved
    3. A comparative study of extra- and intraluminal sigmoid colonic tonometry to detect colonic hypoperfusion after operation for abdominal aortic aneurysm
    Open this publication in new window or tab >>A comparative study of extra- and intraluminal sigmoid colonic tonometry to detect colonic hypoperfusion after operation for abdominal aortic aneurysm
    2011 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 42, no 3, p. 302-308Article in journal (Refereed) Published
    Abstract [en]

    Objectives: There is no ideal method to monitor colonic perfusion after abdominal aortic aneurysm (AAA) repair. The aim was to evaluate extraluminal sigmoid colon tonometry, comparing with the established intraluminal method.

    Methods: Eighteen patients were monitored with both methods, 10 after elective and eight after ruptured AAA repair. One tonometric catheter was placed inside the sigmoid colon (intraluminal) and another extraluminally in close contact with the serosa of the sigmoid colon (extraluminal). Intra- and extraluminal partial pressure of carbon dioxide (pCO2) were measured every 10 min during 48 h postoperatively, 1536 simultaneous measurements. Intraluminal pH (pHi) and extraluminal pH (pHe) were calculated, and intra-abdominal pressure (IAP) was measured, every 4 h. Colonic ischaemia was defined as pHi ≤ 7.1.

    Results: Mean pHi was 7.18 ± 0.11 and mean pHe was 7.28 ± 0.09. With a pHe cut-off value of ≤7.2, the sensitivity and specificity to detect colonic ischaemia were 95% and 95%, respectively. Accuracy was 95% and the positive and negative predictive values 0.80 and 0.99, respectively. The positive likelihood ratio was 19 and the negative likelihood ratio 0.05.

    Conclusion: Extraluminal tonometry may serve as a screening test: A pHe-value <7.2 indicates suspected colonic ischaemia, meriting further investigation. It was not able to evaluate the severity of ischaemia.

    Keywords
    Tonometry, CO2 partial pressure, Colonic ischaemia, Abdominal aortic aneurysm, Rupture, Intra-abdominal pressure, Intra-abdominal hypertension
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-149614 (URN)10.1016/j.ejvs.2011.05.002 (DOI)000295061800006 ()
    Available from: 2011-03-21 Created: 2011-03-21 Last updated: 2017-12-11Bibliographically approved
    4. Intra-abdominal Hypertension and Abdominal Compartment Syndrome after Endovascular Repair of Ruptured Abdominal Aortic Aneurysm
    Open this publication in new window or tab >>Intra-abdominal Hypertension and Abdominal Compartment Syndrome after Endovascular Repair of Ruptured Abdominal Aortic Aneurysm
    2011 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 41, no 6, p. 742-747Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To investigate the frequency of intra-abdominal hypertension (IAH)and abdominal compartment syndrome (ACS) after endovascular repair (EVAR) of rupturedabdominal aortic aneurysm (rAAA).Methods: This was a prospective clinical study. Patients with endovascular repair of rAAAbetween April 2004 and May 2010 were included. Intra-abdominal pressure (IAP) was measuredin the bladder every 4 h. IAH and ACS were defined according to the World Society of theAbdominal Compartment Syndrome consensus document. Early conservative treatments(diuretics, colloids and neuromuscular blockade) were given to patients with IAP > 12 mmHg.Results: Twenty-nine patients, who underwent endovascular repair of a rAAA, had their IAPmonitored. Twenty-five percent of them were in shock at arrival. Postoperatively, 10/29(34%) patients had an IAP > 15 mmHg and six (21%) had an IAP > 20 mmHg. Three (3/29,10%) patients developed ACS that necessitated abdominal decompression in two. Five out ofsix patients with IAP > 20 mmHg presented with preoperative shock. All patients except onewith preoperative shock developed some degree of IAH.Conclusion: IAH and ACS are common and potential serious complications after EVAR for rAAA.Successful outcome depends on early recognition, early conservative treatment to reduce IAHand decompression laparotomy if ACS develops.

    Keywords
    Intra-abdominal pressure, Intra-abdominal hypertension, Abdominal compartment syndrome, Abdominal aortic aneurysm, Rupture, Endovascular repair
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-149613 (URN)doi:10.1016/j.ejvs.2011.02.021 (DOI)000291840900007 ()
    Available from: 2011-03-21 Created: 2011-03-21 Last updated: 2017-12-11Bibliographically approved
  • 249.
    Donoso, Felipe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Engstrand Lilja, Heléne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Risk Factors for Anastomotic Strictures after Esophageal Atresia Repair: Prophylactic Proton Pump Inhibitors Do Not Reduce the Incidence of Strictures2017In: European journal of pediatric surgery, ISSN 0939-7248, E-ISSN 1439-359X, Vol. 27, no 1, p. 50-55Article in journal (Refereed)
    Abstract [en]

    Background: Since 2005, infants with esophageal atresia (EA) in our unit are given prophylactic proton pump inhibitors (PPI) after repair until 1 year of age. The aims of this study were to identify risk factors for anastomotic strictures (AS) and to assess the efficacy of postoperative PPI prophylaxis in reducing the incidence of AS compared with symptomatic PPI. Methods Patients who underwent EA repair from 1994 to 2013 in our unit were included in this retrospective observational study approved by the local ethics review board. They were divided into two subgroups; symptomatic PPI-group with EA repair from 1994 to 2004 and prophylactic PPI-group with EA repair from 2005 to 2013. Data were collected from the patient records. Potential risk factors for AS analyzed were gender, long gap EA, birth weight, premature birth (< 37 gestational weeks), anastomotic tension, and anastomotic leakage. Number of dilatations until the age of 1 and 5 years were recorded. To evaluate risk factors for AS and the effect of prophylactic PPI Logistic, Cox and Poisson regression models were used. For descriptive statistics Fisher exact test and Wilcoxon rank sum test were used. Results A total of 128 patients were included. Patient characteristics, surgical method, grading of anastomotic tension, complications, and survival rates did not differ significantly between the symptomatic PPI-group (n = 71) and the prophylactic PPI-group (n = 57). Comparing the symptomatic and prophylactic PPI-group, there was no significant difference in the median age at the first AS (9.3 vs 6 mo), the number of dilatations until 1 year (2 vs 2) and 5 years (5 vs 4), or the incidence of anastomotic stricture (56.5% vs 50.9%). Long gap EA, high birth weight, and anastomotic tension were found to be independent risk factors. Conclusion Surgeons should aim to perform anastomosis under less tension at EA repair. Prophylactic PPI-treatment does not appear to reduce the rate of AS. Randomized controlled trials with larger study populations are needed to further evaluate the efficacy of prophylactic PPI.

  • 250.
    Donoso, Felipe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Kassa, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Gustafson, Elisabet K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Outcome and management in infants with esophageal atresia: a single centre observational study2016In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 51, no 9, p. 1421-1425Article in journal (Refereed)
    Abstract [en]

    Background/Purpose: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre.

    Methods: Medical records of infants with repaired EA from 1994 to 2013 were reviewed.

    Results: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n = 13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned.

    Conclusion: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.

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Output format
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  • asciidoc
  • rtf