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  • 1.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lundberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors2008In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 32, no 5, p. 930-938Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.

    METHODS:

    Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.

    RESULTS:

    Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.

    CONCLUSIONS:

    Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.

  • 2.
    Frühling, Petter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 4, p. 751-757Article in journal (Refereed)
    Abstract [en]

    Introduction: A single-center nonrandomized clinical trial was performed to assess the safety and efficacy of IRE ablation of liver tumors in humans.

    Methods: 38 malignant liver tumors on 30 patients were treated with IRE between September 2011 and September 2014. Treatment was with curative intent, and the diagnoses were colorectal cancer with liver metastases (CRLM) (n = 23), hepatocellular carcinoma (HCC) (n = 8) and other metastasis (n = 7). Patients were selected when surgery, radiofrequency ablation (RFA) or microwave ablation (MWA) was not an option, and when they met inclusion criteria (tumor size < 3 cm, 1-2 tumors). Patients were followed-up at 1 and 6 months with a contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound (CE-US) at 3 months.

    Results: Ablation success was defined as no evidence of residual tumor in the ablated area as confirmed by CE-CT and CE-US. At 3 months ablation success was 78.9%, and 65.8% at 6 months. There was no statistically significant difference between tumor volume (<5 cm(3) vs >5 cm(3), p = 0.518), and between diagnosis (CRLM vs HCC, p = 0.084) in terms of local recurrence. Complications were classified according to the standardized grading system of Society of Interventional Radiology (SIR). A minor complication occurred in six palients (20%), one patient (3.3%) suffered from a major complication (bile duct dilatation and stricture of the portal vein and bile duct). No mortalities occurred at 30 days.

    Conclusions: IRE appears to be a safe treatment modality for a selected group of patients with liver tumors and offers high local tumor control at 3 and 6 months.

  • 3.
    Krause, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ultrasonography findings and tumour quantification in patients with pseudomyxoma peritonei2012In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 81, no 4, p. 648-651Article in journal (Refereed)
    Abstract [en]

    Pseudomyxoma peritonei (PMP) is a disease with various clinical presentations and the diagnostic value of ultrasonography (US) is under investigated. The purpose of this study was to identify the most common US finding in PMP and to investigate US sensitivity, specificity, positive and negative predictive value in quantifying tumour burden in different abdomino-pelvic regions in PMP patients. Between February 2006 and December 2008, 54 patients were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) due to PMP. The results from preoperative US examination with and without intravenously administrated contrast (SonoVue) were compared to surgical findings. The mean US peritoneal cancer index (PCI) was 6 (range 0-25) and the surgical PCI was 18 (range 3-27) p<0.0001. The histo-pathological subtypes did not influence the US findings. Ascites, bowel loops adhesions and omental cake were mostly visualised correctly by US. The sensitivity of US in quantification of tumour nodules was 91.5% (range 74-100%) and specificity was 33.8% (range 18-55%). The positive predictive value of US examination in PMP was 22% (range 11-44%) and the negative predictive value was 93% (range 77-100%). US can detect the most common PMP findings (ascites and omental cake). The sensitivity of US to quantify PMP tumour burden in different abdominio-pelvic region was relatively high, however, this imaging tool had low specificity.

  • 4. Lorén, I
    et al.
    Lasson, A
    Fork, T
    Genell, S
    Nilsson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Nilsson, P
    Nirhov, N
    New sonographic imaging observations in focal pancreatitis.1999In: Eur Radiol, ISSN 0938-7994, Vol. 9, no 5, p. 862-7Article in journal (Other scientific)
  • 5.
    Loskog, Angelica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Maleka, Aglaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mangsbo, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Svensson, Emma
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Lundberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Agnarsdóttir, Margrét
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tötterman, Thomas H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients2016In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 8, p. 872-880Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.

    METHODS: AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.

    RESULTS: AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.

    CONCLUSIONS: AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.

  • 6.
    Magnusson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Geterud, Kjell
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lindqvist, Klas
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nyman, Ulf
    Hellström, Mikael
    Ultraljud vs DT vid uretärsten: svenska rutiner gäller2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 49-50, p. 2236-2237Article in journal (Other academic)
  • 7.
    Månsson, Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bergenfeldt, Magnus
    Brahmstaedt, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 1A, p. 289-293Article in journal (Refereed)
    Abstract [en]

    Background:

    Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase I study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC).

    Patients and Methods:

    Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation.

    Results:

    No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound.

    Conclusion:

    IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.

  • 8.
    Månsson, Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Månsson, Daniel
    Royal Inst Technol KTH, Sch Elect Engn, Stockholm, Sweden..
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Response from the authors of the original article. Comment to: Mansson C, Nilsson A, Karlson B-M. Severe complications with irreversible electroporation of the pancreas in the presence of a metallic stent: a warning of a procedure that never should be performed2015In: ACTA RADIOLOGICA OPEN, ISSN 2058-4601, Vol. 4, no 9, article id UNSP 2058460115603876Article in journal (Other academic)
  • 9.
    Nilsson, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Lorén, I
    Nirhov, N
    Lindhagen, T
    Nilsson, P
    Power Doppler ultrasonography: alternative to computed tomography in abdominal trauma patients.1999In: J Ultrasound Med, ISSN 0278-4297, Vol. 18, no 10, p. 669-72Article in journal (Other scientific)
  • 10.
    Nilsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Contrast-enhanced ultrasound of the kidneys.2004In: Eur Radiol, ISSN 0938-7994, Vol. 14 Suppl 8, p. P104-9Article in journal (Refereed)
  • 11.
    Norlén, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    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.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    11C-5-hydroxytryptophan positron emission tomography after radiofrequency ablation of neuroendocrine tumor liver metastases2012In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, no 6, p. 883-890Article in journal (Refereed)
    Abstract [en]

    Aim: The aim was to assess the feasibility of C-11-5-hydroxy-tryptophan positron emission tomography ( C-11-5-HTP-PET) in the follow-up after radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumors (NETS). Background: Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound (CEUS) are commonly used to evaluate the liver after RFA of NETs. In general, C-11-5-HTP-PET is more sensitive in the visualization of NETs, but no studies have investigated its role after RFA.

    Methods: Six consecutive patients with liver metastases from NETs were subjected to RFA treatment. All patients underwent baseline imaging before RFA and on two occasions (1-2 and 6-11 months) after RFA. The imaging consisted of C-11-5-HTP-PET, CEUS and CECT on all three occasions.

    Results: Thirty RFA areas were evaluated, and residual tumors (RTs) were depicted in eight areas (22%). C-11-5-HTP-PET depicted RTs after RFA with maximum sensitivity (100%) and specificity (100%), using radiological follow-up as the gold standard. C-11-5-HTP-PET detected five out of eight RTs earlier than CECT or CEUS. In general, the sensitivity of C-11-5-HTP-PET exceeded that of CECT and CEUS for early visualization of NET liver metastases.

    Conclusion: C-11-5-HTP-PET can be used in the follow-up after RFA for the purpose of detecting RT, and it provides additional information to CEUS and CECT by detecting new lesions.

  • 12.
    Schiza, Aglaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wenthe, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mangsbo, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tötterman, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Loskog, Angelica S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Adenovirus-mediated CD40L gene transfer increases teffector/tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 337-337Article in journal (Other academic)
  • 13.
    Sällström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Peuckert, Christiane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Gao, Xiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Jensen, Boye L.
    Onozato, Maristela L.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Carlström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension2013In: AM J PHYSIOL-RENAL, ISSN 1931-857X, Vol. 305, no 1, p. F71-F79Article in journal (Refereed)
    Abstract [en]

    Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein (EphA4(gf/gf)), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4(gf/gf) mice and littermate controls (EphA4(+/+)) during normal (0.7% NaCl)- and high (4% NaCl)-sodium conditions. Renal excretion, renal plasma flow, and glomerular filtration were studied, and histology and morphology of the kidneys and ureters were performed. EphA4(gf/gf) mice developed variable degrees of hydronephrosis that correlated with their blood pressure level. In contrast to EphA4(+/+), the EphA4(gf/gf) mice displayed salt-sensitive hypertension, reduced urine concentrating ability, reduced renal plasma flow, and lower glomerular filtration rate. Kidneys from EphA4(gf/gf) mice showed increased renal injuries, as evidenced by fibrosis, inflammation, and glomerular and tubular changes. In conclusion, congenital hydronephrosis causes hypertension and renal damage, similar to that observed in experimentally induced hydronephrosis. This study further reinforces the supposed causal link between hydronephrosis and later development of hypertension in humans.

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