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  • 101.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Persisting disturbances in calcium homeostasis after gastric bypass surgeryManuskript (preprint) (Övrigt vetenskapligt)
  • 102.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stevens, Katharina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study2018Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, nr 10, s. 3007-3011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: By treating obesity, one of the major epidemics of this past century, through bariatric surgery, we may cause complications due to malnourishment in a growing population. At present, vitamin D deficiency is of interest, especially in patients with inferior absorption of fat-soluble nutrients after biliopancreatic diversion with duodenal switch (BPD/DS).

    Methods: Twenty BPD/DS patients, approximately 4 years postoperatively, were randomized to either intramuscular supplementation of vitamin D with a single dose of 600,000 IU cholecalciferol, or a control group. Patients were instructed to limit their supplementation to 1400 IU of vitamin D and to avoid the influence of UV-B radiation; the study was conducted when sunlight is limited (December to May).

    Results: Despite oral supplementation, a pronounced deficiency in vitamin D was seen (injection 19.3; control 23.2 nmol/l) in both groups. The cholecalciferol injection resulted in elevated 25[OH]D levels at 1 month (65.4 nmol/l), which was maintained at 6 months (67.4 nmol/l). This resulted in normalization of intact parathyroid hormone (PTH) levels. No changes in vitamin D or PTH occurred in the control group.

    Conclusions: In BPD/DS patients, having hypovitaminosis D despite full oral supplementation, a single injection of 600,000 IU of cholecalciferol was effective in elevating vitamin D levels and normalizing levels of intact PTH. The treatment is simple and highly effective and thus recommended, especially in cases of reduced UV-B radiation.

  • 103.
    Hultman, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Gunnarsson, Ulf
    Karolinska Institutet, Institutionen för kirurgisk vetenskap, intervention och teknik, Stockholm, Sverige.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    A population-based study of incidence of peritoneal metastases and prognostic factors in patients with loco-regionally advanced gastric cancerManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Purpose   The aim was to investigate epidemiological and prognostic factors as a knowledge base for the treatment of patients with loco-regionally advanced gastric cancer (GC). Methods   In Uppsala County between 2000 and 2009, two hundred and fifty-five patients with GC were identified. Data from patient records were analyzed for loco-regionally advanced GC, defined as tumor invading the parietal and/or visceral peritoneum, including peritoneal metastasis but excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. Presence or absence of distant metastasis (DM) in these patients was also assessed. Results   One hundred and twenty patients (47% of all patients with GC) experienced loco-regionally advanced disease. Forty-one percent also had DM. Median overall survival (mOS) from diagnosis of local-regionally advanced disease was 4.8 months for the whole group of patients, 5.1 months for the subgroup of patients without DM and 4.7 months for the subgroup with DM. Using multivariate Cox analysis, positive prognostic factors for survival identified were good performance status and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative predictive factor. The mOS did not differ between the first and second time period. Discussion   Peritoneal metastasis from GC is more common than previously reported. The lack of improvement in OS over the past decade signals a need for new treatment strategies.

  • 104.
    Hultman, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Gunnarsson, Ulf
    Umea Univ, Dept Surg & Perioperat Sci, SE-90185 Umea, Sweden.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Prognostic factors in patients with loco-regionally advanced gastric cancer2017Ingår i: World Journal of Surgical Oncology, ISSN 1477-7819, E-ISSN 1477-7819, Vol. 15, artikel-id 172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate epidemiologic and prognostic factors relevant to the treatment of loco-regionally advanced gastric cancer (GC).

    METHODS: Two hundred and fifty-five patients with GC were identified in Uppsala County between 2000 and 2009. Patient records were analyzed for loco-regionally advanced GC defined as tumor with peritoneal involvement, excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. The presence or not of distant metastasis (DM), including hematogenous metastases (e.g., liver, lung, and bone) and/or distant lymph node metastases, was also analyzed. The Cox proportional hazard model was used for multivariate analysis of factors influencing survival.

    RESULTS: One hundred and twenty patients (47% of all patients with GC; median age 70.5 years) had loco-regionally advanced disease, corresponding to an incidence of 3.8 per 100,000 person-years. Forty-one percent of these also had DM. Median overall survival (mOS) from the time of the diagnosis of loco-regionally advanced disease was 4.8 months for the total patient cohort, 5.1 months for the subgroup of patients without DM, and 4.7 months for the subgroup with DM. There was no significant difference in mOS between the subgroups with synchronous versus metachronous loco-regionally advanced GC: 4.8 months (range 0.0-67.4) versus 4.7 months (range 0.0-28.3). Using multivariate Cox analysis, positive prognostic factors for survival were good performance status at diagnosis and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative prognostic factor. The mOS did not differ when comparing the time period 2000-2004 (5.1 months, range 0-67.4) with the period 2005-2009 (4.0 months, range 0.0-28.3).

    CONCLUSION: Peritoneal involvement occurred in almost half of the patients with GC in this study and was associated with short life expectancy. New treatment strategies are warranted.

  • 105.
    Hultman, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Lind, Pehr
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Haglund, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy2013Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, nr 4, s. 824-830Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.

    Material and methods

    Eighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.

    Results

    At the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.

    Discussion

    Neoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.

  • 106.
    Hultman, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Ljungman, Martin
    Västmanlands sjukhus, Kirurgkliniken, Västerås, Sverige.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy2014Ingår i: Journal of Experimental & Clinical Cancer Research, ISSN 1756-9966, E-ISSN 1756-9966, Vol. 33, artikel-id 110Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background  

    The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.

    Methods  

    Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mito­mycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.

    Results    

    The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.

    Conclusion    

    Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.

  • 107.
    Isacson, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Treatment of Acute Uncomplicated Colonic Diverticulitis2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The overall aim of this thesis was to evaluate the clinical management of AUD with regard to the no-antibiotic policy and its long-term effect, treatment on an outpatient basis and the potential health-care cost savings

    Study I:  a retrospective study at Västmanlands Hospital that evaluated and confirmed the adherence to the no-antibiotic policy in patients with AUD and its safety regarding complications and recurrences. A total of 246 patients with acute diverticulitis were identified, of which 195 had computed tomography (CT) confirmed AUD. In total, 91.3% of these patients did not receive any antibiotics and only two developed complications.

    Study II: a retrospective study with the aim to conduct a long-term follow-up of all Swedish patients who participated in the AVOD trial in terms of recurrences, complications, surgery and quality of life. The medical records of 96% of the patients were reviewed with a mean follow up of 11 years. Quality of life questionnaires were sent out to all patients. There were no differences regarding the rates of recurrence, complications or surgery for diverticulitis. There were no differences in the quality of life between groups according to the EQ-5D questionnaire.

    Study III: a prospective study where 155 patients with CT-verified AUD as were treated as outpatients without antibiotics. On day 3, patients reported an average pain score of 1.8 of 10 on the VAS scale and only 30% of patients were using analgesia. Four patients returned to hospital because of treatment failure.

    Study IV: a retrospective cohort study at Västmanland’s Hospital evaluated the impact on admissions, complication rates and health-care costs of the policy of outpatient treatment without using antibiotics. Medical records of all patients diagnosed with AUD in the year before (2011) and after (2014) the implementation of outpatient management without antibiotics were reviewed. Overall 494 episodes of AUD were identified: 254 in 2011 and 240 in 2014. Three patients developed complications in 2011 and four in 2014. The proportion of patients managed as outpatients was 20% in 2011 compared with 61% in 2014. The hospital admissions, total length of stay of and total health-care costs were almost halved.

    In conclusion, these studies confirm the low complication and recurrence rates of AUD and strengthens findings that antibiotics have no benefit in the treatment of this disease. The no-antibiotic policy had no impact on short- or long-term outcomes regarding the rates of recurrence, complications, surgery or quality of life. Outpatient management was found to be feasible and safe, and significantly reduced admissions, which led to large health-care cost savings.

    Delarbeten
    1. No antibiotics in acute uncomplicated diverticulitis: does it work?
    Öppna denna publikation i ny flik eller fönster >>No antibiotics in acute uncomplicated diverticulitis: does it work?
    Visa övriga...
    2014 (Engelska)Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, nr 12, s. 1441-1446Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background. The first randomized multicenter study evaluating the need for antibiotic treatment in patients with acute uncomplicated diverticulitis (AUD) could not demonstrate any benefit gained from antibiotic use. The aim of this study was to review the application of the no antibiotic policy and its consequences in regard to complications and recurrence. Methods. This retrospective population-based cohort study included all patients diagnosed with all types of colonic diverticulitis during the year 2011 at Vastmanland Hospital Vasteras, Sweden. All medical records were carefully reviewed. Primary outcomes were the types of treatment adopted for diverticulitis, complications and recurrence. Results. In total, 246 patients with computer tomography-verified diverticulitis were identified, 195 with primary AUD and 51 with acute complicated diverticulitis. Age, sex, and temperature at admission were similar between the groups but there was a significant difference in white blood cell count, C-reactive protein, and length of hospital stay. In the AUD group, 178 (91.3%) patients were not treated with antibiotics. In this group, there were six (3.4%) readmissions but only two developed an abscess. Of the remaining 17 patients (8.7%) who were treated with antibiotics in the AUD group, one developed an abscess. Twenty-five (12.8%) patients in the AUD group presented with a recurrence within 1 year. Conclusion. The no-antibiotic policy for AUD is safe and applicable in clinical practice. The previous results of a low complication and recurrence rate in AUD are confirmed. There is no need for antibiotic treatment for AUD. What does this paper add to the literature? Despite published papers with excellent results, there are still doubts about patient safety against the policy to not use antibiotics in acute uncomplicated diverticulitis. This is the first paper, in actual clinical practice, to confirm that the no antibiotic policy for acute uncomplicated diverticulitis is applicable and safe.

    Nyckelord
    antibiotics, colonic diverticulitis, complications
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:uu:diva-240083 (URN)10.3109/00365521.2014.968861 (DOI)000345603500007 ()25369865 (PubMedID)
    Tillgänglig från: 2015-01-05 Skapad: 2015-01-05 Senast uppdaterad: 2018-12-10Bibliografiskt granskad
    2. Antibiotic avoidance in patients with acute uncomplicated diverticulitis: ten-year follow-up of a randomized clinical trial
    Öppna denna publikation i ny flik eller fönster >>Antibiotic avoidance in patients with acute uncomplicated diverticulitis: ten-year follow-up of a randomized clinical trial
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nyckelord
    Diverticulitis, antibiotics, recurrent diverticulitis, sigmoidectomy
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-369127 (URN)
    Tillgänglig från: 2018-12-10 Skapad: 2018-12-10 Senast uppdaterad: 2018-12-20
    3. Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study
    Öppna denna publikation i ny flik eller fönster >>Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study
    Visa övriga...
    2015 (Engelska)Ingår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, nr 9, s. 1229-1234Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The aim of this study was to evaluate outpatient, non-antibiotic management in acute uncomplicated diverticulitis with regard to admissions, complications, and recurrences, within a 3-month follow-up period. A prospective, observational study in which patients with computer tomography-verified acute uncomplicated diverticulitis were managed as outpatients without antibiotics. The patients kept a personal journal, were contacted daily by a nurse, and then followed up by a surgeon at 1 week and 3 months. In total, 155 patients were included, of which 54 were men; the mean age of the patients was 57.4 years. At the time of diagnosis, the mean C-reactive protein and white blood cell count were 73 mg/l and 10.5 x 10(9), respectively, and normalized in the vast majority of patients within the first week. The majority of the patients (97.4 %) were managed successfully as outpatients without antibiotics, admissions, or complications. In only four (2.6 %) patients, the management failed because of complications in three and deterioration in one. These patients were all treated successfully as inpatients without surgery. Five patients had recurrences and were treated as outpatients without antibiotics. Follow-up colonic investigations revealed cancer in two patients and polyps in 13 patients. Previous results of low complication rates with the non-antibiotic policy were confirmed. The new policy of outpatient management without antibiotics in acute uncomplicated diverticulitis is now shown to be feasible, well functioning, and safe.

    Nyckelord
    Diverticulitis, Outpatient management, Antibiotics
    Nationell ämneskategori
    Hälso- och sjukvårdsorganisation, hälsopolitik och hälsoekonomi Klinisk medicin
    Identifikatorer
    urn:nbn:se:uu:diva-262965 (URN)10.1007/s00384-015-2258-y (DOI)000360542000011 ()25989930 (PubMedID)
    Anmärkning

    Correction in: International Journal of Colorectal Disease, 2015, vol. 30, issue 9, pages 1225-1235, doi: 10.1007/s00384-015-2284-9

    Tillgänglig från: 2015-09-24 Skapad: 2015-09-23 Senast uppdaterad: 2018-12-10Bibliografiskt granskad
    4. Outpatient management of acute uncomplicated diverticulitis results in health-care cost savings
    Öppna denna publikation i ny flik eller fönster >>Outpatient management of acute uncomplicated diverticulitis results in health-care cost savings
    Visa övriga...
    2018 (Engelska)Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 4, s. 449-452Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose:

    Outpatient management without antibiotics has been shown to be safe for selected patients diagnosed with acute uncomplicated diverticulitis (AUD). The aim of this study was to evaluate the impact on admissions, complication rates and health-care costs of the policy of outpatient treatment without using antibiotics.

    Methods:

    The medical records of all patients diagnosed with AUD in the year before (2011) and after (2014) the implementation of outpatient management without antibiotics in Vastmanland County were reviewed. Health-care cost analysis was performed using the Swedish cost-per-patient model.

    Results:

    In total, 494 episodes of AUD were identified, 254 in 2011 and 240 in 2014. The proportion of patients managed as outpatients was 20% in 2011 compared with 60% in 2014 (p<.001). There were 203 hospital admissions and a total length of stay of 677 days in 2011 compared with 95 admissions and 344 days in 2014 (both p<.001). The total health-care cost was Euro558,679 in 2011 compared with Euro370,370 in 2014 (p<.001). Three patients developed complications in 2011 and four in 2014 (p=.469).

    Conclusions:

    The new policy of outpatient management without antibiotics in routine health care almost halved the total health-care cost without an increase in the complication rate.

    Nyckelord
    Diverticulitis, outpatient management, antibiotics, health-care costs
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:uu:diva-354262 (URN)10.1080/00365521.2018.1448887 (DOI)000430726600011 ()29543100 (PubMedID)
    Tillgänglig från: 2018-06-28 Skapad: 2018-06-28 Senast uppdaterad: 2018-12-10Bibliografiskt granskad
  • 108.
    Isacson, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Andreasson, Kalle
    Nikberg, Maziar
    Smedh, Kenneth
    Chabok, Abbas
    No antibiotics in acute uncomplicated diverticulitis: does it work?2014Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, nr 12, s. 1441-1446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The first randomized multicenter study evaluating the need for antibiotic treatment in patients with acute uncomplicated diverticulitis (AUD) could not demonstrate any benefit gained from antibiotic use. The aim of this study was to review the application of the no antibiotic policy and its consequences in regard to complications and recurrence. Methods. This retrospective population-based cohort study included all patients diagnosed with all types of colonic diverticulitis during the year 2011 at Vastmanland Hospital Vasteras, Sweden. All medical records were carefully reviewed. Primary outcomes were the types of treatment adopted for diverticulitis, complications and recurrence. Results. In total, 246 patients with computer tomography-verified diverticulitis were identified, 195 with primary AUD and 51 with acute complicated diverticulitis. Age, sex, and temperature at admission were similar between the groups but there was a significant difference in white blood cell count, C-reactive protein, and length of hospital stay. In the AUD group, 178 (91.3%) patients were not treated with antibiotics. In this group, there were six (3.4%) readmissions but only two developed an abscess. Of the remaining 17 patients (8.7%) who were treated with antibiotics in the AUD group, one developed an abscess. Twenty-five (12.8%) patients in the AUD group presented with a recurrence within 1 year. Conclusion. The no-antibiotic policy for AUD is safe and applicable in clinical practice. The previous results of a low complication and recurrence rate in AUD are confirmed. There is no need for antibiotic treatment for AUD. What does this paper add to the literature? Despite published papers with excellent results, there are still doubts about patient safety against the policy to not use antibiotics in acute uncomplicated diverticulitis. This is the first paper, in actual clinical practice, to confirm that the no antibiotic policy for acute uncomplicated diverticulitis is applicable and safe.

  • 109.
    Isacson, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Antibiotic avoidance in patients with acute uncomplicated diverticulitis: ten-year follow-up of a randomized clinical trialIngår i: Artikel i tidskrift (Refereegranskat)
  • 110.
    Jarbrink-Sehgal, M. Ellionore
    et al.
    Dept Med, Solna, Sweden;Baylor Coll Med, Digest Dis Ctr, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA.
    Schmidt, Peter T.
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden;Dept Med, Solna, Sweden.
    Sköldberg, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hemmingsson, Tomas
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Stockholm Univ, Dept Publ Hlth Sci, Stockholm, Sweden.
    Hagstrom, Hannes
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.
    Andreasson, Anna
    Dept Med, Solna, Sweden;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization2018Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 16, nr 9, s. 1474-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. METHODS: We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. RESULTS: Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). CONCLUSIONS: In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later.

  • 111.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Edholm, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rosqvist, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Rudling, Mats
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Straniero, Sara
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements2019Ingår i: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 9, nr 1, artikel-id 34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.7 ± 2.6 kg/m2) whereof 6 had NAFLD. Mean weight loss was 7.4 ± 1.2 kg (0.7 kg/day) and liver fat decreased by 51 ± 16%, resulting in only three subjects having NAFLD at day 28. Marked alteration of insulin, NEFA, ALT and 3-hydroxybuturate was evident 3 days after commencing LCD, whereas liver fat showed a moderate but a linear reduction across the 28 days. Other circulating-liver fat markers (e.g. triglycerides, adiponectin, stearoyl-CoA desaturase-1 index, fibroblast growth factor 21) demonstrated modest and variable changes. Marked elevations of NEFA, 3-hydroxybuturate and ALT concentrations occurred until day 14, likely reflecting increased tissue lipolysis, fat oxidation and upregulated hepatic fatty acid oxidation. In summary, these results suggest linear reduction in liver fat, time-specific changes in metabolic markers and insulin resistance in response to energy restriction.

  • 112.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Alterations in proinsulin and insulin dynamics, HDL Cholesterol and ALT after gastric bypass surgery: A 42-months follow-up study2009Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, nr 5, s. 601-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Roux-en-Y gastric bypass (RYGBP) powerfully reduces type 2 diabetes (T2DM) incidence. Proinsulin predicts development of T2DM. Adjustable gastric banding is associated with lowered proinsulin but after RYGBP information is scant. METHODS: Twenty-one non-diabetic morbidly obese patients who underwent RYGBP surgery were evaluated before (baseline), at 12 months (first follow-up), and at 42 months, range 36-50 (second follow-up), after surgery and compared to a control group, matched at baseline regarding fasting glucose, insulin, proinsulin, alanine aminotransferase (ALT), high-density lipoprotein (HDL) cholesterol, and body mass index (BMI). RESULTS: In the RYGBP group, fasting serum proinsulin concentrations were markedly lowered from 13.5 to 3.5 pmol/l at first follow-up and to 4.9 pmol/l at second follow-up (p < 0.001, respectively). Fasting insulin concentrations were reduced from 83.4 to 24.6 pmol/l at first follow-up (p < 0.001) and to 36.4 pmol/l at second follow-up (p < 0.01). ALT was lowered from 0.62 to 0.34 mukatal/l at first follow-up and continued to lower to 0.24 mukatal/l at second follow-up (p < 0.001, respectively). The further decrease between first and second follow-up was also significant (p = 0.002). HDL cholesterol increased from 1.16 to 1.45 mmol/l at the first follow-up and continued to increase at second follow-up to 1.58 mmol/l (p < 0.001, respectively). The further increase between first and second follow-up was also significant (p = 0.006). The differences between groups at first follow-up were significant for BMI, proinsulin, insulin, ALT, and HDL cholesterol (p = 0.04-0.001). CONCLUSION: RYGBP surgery in morbidly obese patients is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, and ALT and increased HDL cholesterol.

  • 113.
    Johansson, Hans-Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Serum Magnesium Status After Gastric Bypass Surgery in Obesity2009Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 19, nr 9, s. 1250-1255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Roux-en-Y gastric bypass (RYGBP) has become a common surgical procedure to treat morbid obesity. Furthermore, it strongly reduces the incidence of type 2 diabetes and mortality. However, there is scant information on how magnesium status is affected by RYGBP surgery. Previous bariatric surgery methods, like jejunoileal bypass, are associated with hypomagnesemia. METHODS: Twenty-one non-diabetic morbidly obese patients who underwent RYGBP were evaluated before and 1 year after surgery and compared to a matched morbidly obese control group regarding serum magnesium. Groups were matched regarding weight, BMI, abdominal sagittal diameter and fasting glucose, blood pressure, and serum magnesium concentrations before surgery in the RYGBP group. RESULTS: The serum magnesium concentrations increased by 6% from 0.80 to 0.85 mmol/l (p = 0.019) in the RYGBP group while a decrease by 4% (p = 0.132) was observed in the control group. The increase in magnesium concentration at the 1-year follow-up in the RYGBP group was accompanied by a decreased abdominal sagittal diameter (r (2) = 0.32, p = 0.009), a lowered BMI (r (2) = 0.28, p = 0.0214), a lowered glucose concentration (r (2) = 0.28, p = 0.027) but not by a lowered insulin concentration (p = 0.242), a lowered systolic (p = 0.789) or a lowered diastolic (p = 0.785) blood pressure. CONCLUSION: RYGBP surgery in morbidly obese subjects is characterized by reduced visceral adiposity, lowered plasma glucose, and increased circulating magnesium concentrations. The inverse association between lowered central obesity, lowered plasma glucose and increased magnesium concentrations, needs further detailed studies to identify underlying mechanisms.

  • 114.
    Johansson, H.-E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Edén Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, F. Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion2007Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 24, nr 11, s. 1213-1220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). Methods Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) ± SD, 34.8 ± 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 ± 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 ± 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. Results Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). Conclusions MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.

  • 115.
    Johansson, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Roos, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Edén Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy2008Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 18, nr 10, s. 1297-1304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

  • 116.
    Kakoulidis, Thanos P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi. Ctr Minimally Invas Surg, Stockholm, Sweden.
    Arvidsson, Dag
    Ctr Minimally Invas Surg, Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Reduced Need for In-hospital Care After Sleeve Gastrectomy: a Single Center Observational Study2019Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, nr 10, s. 3228-3231Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Setting

    Private clinic, Stockholm, and nation-wide in-hospital care, Sweden.

    Objectives

    The use of sleeve gastrectomy (SG) for treatment of morbid obesity has increased worldwide, but information about long-term outcome is still limited. Our objective was to evaluate the need for additional in-hospital care after SG for obesity (body mass index [BMI] >30) in 862 patients, all operated at a single center.

    Methods

    Two national registries, the Inpatient Registry and the Death Registry, were used to collect long-term data on in-hospital care, grouped by the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and mortality, respectively.

    Results

    In-hospital care for SG-operated females was decreased for four groups of obesity-related ICD-10 diagnoses: endocrine and metabolic diseases and circulatory, digestive, and genitourinary diseases, as well as injuries and poisoning (p<0.001 for all). However, female SG patients still required in-hospital care above the national level for women of corresponding ages.

    Conclusions

    Although a significant reduction in in-hospital care was observed, SG patients did not reach national levels.

  • 117.
    Kalliomäki, Maija-L
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sandblom, Gabriel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Gunnarsson, U.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Persistent pain after groin hernia surgery: a qualitative analysis of pain and its consequences for quality of life2009Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, nr 2, s. 236-246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite a high prevalence of persistent groin pain after hernia repair, the specific nature of the pain and its clinical manifestation are poorly known. The aim of this study was to determine the type of post-herniorrhaphy pain and its influence on daily life. In order to assess long-term pain qualitatively and to explore how it affects quality of life, 100 individuals with persisting pain, identified in a cohort study of patients operated for groin hernia, were neurologically examined, along with 100 pain-free controls matched for age, gender and type of operation. The patients were asked to answer the SF-36 questionnaire, the hospital anxiety and depression scale, the Swedish Scales of Personality (SSP) and a standardised questionnaire for assessing everyday life coping. The patients were approached approximately 4.9 years after surgery. Twenty-two patients from the pain group had become pain free by the time of examination, whereas 76 patients still had pain, of whom 47 (68%) suffered from neuropathic pain and 11 from nociceptive pain. The remaining patients suffered from mixed pain, neuropathic and nociceptive, or were found to have another reason for pain. All dimensions of SF-36 were poorer for the pain group than the control group. Persistent post-herniorrhaphy pain is mainly neuropathic and has a substantial impact on health-related quality of life.

  • 118.
    Kamble, Prasad G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sidibeh, Cherno O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Amini, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Börjesson, Joey Lau
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue2016Ingår i: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 427, s. 124-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPAR gamma and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess.

  • 119.
    Kamble, Prasad G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria João
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sidibeh, Cherno O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Amini, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Role of lipocalin 2 in human adipose tissue metabolism and glucocorticoid-induced insulin resistance2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S321-S321Artikel i tidskrift (Övrigt vetenskapligt)
  • 120. Karefylakis, Christos
    et al.
    Näslund, Ingmar
    Edholm, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Karlsson, F Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rask, Eva
    Prevalence of Anemia and Related Deficiencies 10 Years After Gastric Bypass: a Retrospective Study2015Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, nr 6, s. 1019-1023Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Bariatric surgery has gained wide acceptance as treatment for severe obesity and is associated with decreased overall mortality. The aims of this study were to evaluate the prevalence of anemia long term after Roux-en-Y gastric bypass (RYGB) and to search for factors predicting anemia.

    METHODS:

    All 745 patients who underwent RYGB between 1993 and 2003 at either Örebro or Uppsala University Hospital and who were living in Sweden were invited to participate by providing a fasting blood sample and completing a questionnaire about their health status. Full blood count, serum iron, transferrin, vitamin B12, and folic acid were determined.

    RESULTS:

    Follow-up was completed in 431 patients (58 %) with mean age 51.3 ± 10 years. Of all patients, 27 % had anemia postoperatively and related deficiencies; iron, folic acid, and vitamin B12 were seen in 20, 12, and 2 %, respectively. There was no correlation between anemia and sex, follow-up time, 25-OH vitamin D level, and preoperative or postoperative BMI. An inverse correlation was found between anemia and regular medical checkups concerning gastric bypass surgery.

    CONCLUSION:

    Twenty-seven percent of patients had anemia more than 10 years after RYGB. Anemia does not seem to progress with time and was less common in patients with regular medical checkups. Thus, improved long-term follow-up is needed.

  • 121. Karefylakis, Christos
    et al.
    Näslund, Ingmar
    Edholm, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Karlsson, F Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rask, Eva
    Vitamin D Status 10 Years After Primary Gastric Bypass: Gravely High Prevalence of Hypovitaminosis D and Raised PTH Levels2014Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 24, nr 3, s. 343-348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    The primary aim of this study was to evaluate the prevalence of vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass. Secondly, we have tried to assess predictors for vitamin D deficiency.

    METHODS

    Five hundred thirty-seven patients who underwent primary Roux-en-Y gastric bypass surgery between 1993 and 2003 at the Örebro University Hospital and Uppsala University Hospital were eligible for the study. Patients were asked to provide a blood sample between November 2009 and June 2010 and to complete a questionnaire about their postoperative health status. Serum values of 25-OH vitamin D, parathyroid hormone (PTH), alkaline phosphatase (ALP) and calcium were determined.

    RESULTS

    Follow-up was completed in 293 patients, of which 83 % were female, with an age of 49 ± 9.9 years after a median time of 11 ± 2.8 years. Vitamin D, PTH and albumin-corrected calcium values were 42 ± 20.4 nmol/L, 89.1 ± 52.7 ng/L and 2.3 ± 0.1 mmol/L, respectively. Of all patients, 65 % were vitamin D deficient, i.e. 25-OH vitamin D <50 nmol/L, and 69 % had PTH above the upper normal reference range, i.e. >73 ng/L. Vitamin D was inversely correlated with PTH levels (p < 0.001) and positively correlated with calcium (p = 0.016). Vitamin D did not correlate with ALP. The only factor found to predict vitamin D deficiency was high preoperative body mass index (BMI) (p = 0.008), whereas gender, age, time after surgery and BMI at follow-up did not.

    CONCLUSIONS

    Vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass (RYGB) were confirmed in our study because 65 % of patients had vitamin D deficiency, and 69 % had increased PTH levels more than 10 years after surgery. These data are alarming and highlight the need for improved long-term follow-up. Vitamin D deficiency does not seem to progress with time after surgery, possibly due to weight loss. Only preoperative BMI, cutoff point 43 kg/m(2), was a predictor of vitamin D deficiency at follow-up. Improved long-term follow-up of patients that undergo RYGB is needed.

  • 122.
    Karlgren, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Vildhede, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Norinder, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Wisniewski, Jacek R.
    Kimoto, Emi
    Lai, Yurong
    Haglund, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug - Drug Interactions2012Ingår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, nr 10, s. 4740-4763Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1, The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.

  • 123.
    Karlgren, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Vildhede, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Ölander, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Wisniewski, Jacek
    Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany..
    Norén, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Global Membrane Protein Analysis Of The Human Liver: Application In Predictions Of Atorvastatin Uptake Clearance2015Ingår i: Drug metabolism reviews (Softcover ed.), ISSN 0360-2532, E-ISSN 1097-9883, Vol. 47, s. 245-246Artikel i tidskrift (Övrigt vetenskapligt)
  • 124.
    Karlsson, Britt-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi.
    Andersson Forsman, Catarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Wilander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lindgren, Per-Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Jacobson, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi.
    Rastad, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Efficiency of percutaneous core biopsy in pancreatic tumor diagnosis1996Ingår i: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 120, nr 1, s. 75-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Radiologic diagnosis of pancreatic tumors exhibits limited precision. The aim of this study was to investigate the outcome and complications of pancreatic core biopsy in patients with suspected pancreatic neoplasms.

    METHODS:

    One hundred patients underwent ultrasonography-guided core biopsy of 1.2 mm external diameter. Medical charts were examined for biochemical and clinical signs of complications. Final diagnosis was settled by operation, autopsy, and clinical signs of the disease including survival with at least 2.3 years of follow-up.

    RESULTS:

    Histopathologic biopsy evaluation showed correct discrimination between exocrine and endocrine tumors and nonneoplastic conditions in 89 patients. No false-positive cancer diagnosis was found, and guidance on nature of primary tumors was obtained for eight of eight metastases. The sensitivity was 91% for exocrine and 87% for endocrine pancreatic tumors, and negative predictive values of these diagnoses were 83% and 97%, respectively. No clinically significant complications were noted.

    CONCLUSIONS:

    Core biopsy is an attractive alternative to diagnostic laparotomy in unresectable pancreatic cancer and efficiently provides diagnosis of endocrine tumors and pancreatic metastases in conjunction with rare complications. Benign biopsy findings cannot be used to exclude presence of primary or metastatic pancreatic neoplasms.

  • 125.
    Katsogiannos, Petros
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Boersma, Greta J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundkvist, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Glucose homeostasis and whole-body insulin resistance improved 4 weeks after gastric bypass surgery in type 2 diabetes, whereas adipose tissue metabolism was unchanged2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr S1, s. S253-S254, artikel-id 557Artikel i tidskrift (Övrigt vetenskapligt)
  • 126.
    Katsogiannos, Petros
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kamble, Prasad G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Boersma, Greta J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Karlsson, F. Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundkvist, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D2019Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 7, s. 2601-2613Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance.

    Objective: To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D.

    Design and Setting: A randomized single-center study.

    Patients: Nineteen patients with T2D with body mass index 30 to 45 kg/m(2).

    Interventions: Thirteen patients were assessed at baseline and 4 and 24 weeks after RYGB (preceded by a 4-week low-calorie diet) and compared with 6 control patients continuing standard medical treatment: oral glucose tolerance test, subcutaneous AT biopsies for gene expression, adipocyte size, glucose uptake, lipolysis, and insulin action.

    Results: At 4 and 24 weeks post-RYGB, all patients but one had stopped diabetes medication. Fasting glucose, HbA(1c), and insulin levels decreased and the Matsuda index increased compared with baseline (P < 0.01 for all), indicating improved whole-body insulin sensitivity. Mean adipocyte size significantly reduced, more at 4 than at 24 weeks; at 4 weeks, glucose uptake per adipocyte was lowered, and isoproterenol-stimulated lipolysis tended to increase, whereas the fold insulin effects on glucose uptake and lipolysis were unchanged. Expression of genes involved in fatty acid oxidation, CPT1b and adiponectin, was increased at 4 weeks, whereas leptin and E2F1 (involved in cell proliferation) were reduced (P < 0.05 for all).

    Conclusion: Glycemic control and in vivo insulin sensitivity improved 4 weeks after RYGB, but adipocyte insulin sensitivity did not change despite a marked reduction in adipocyte size. Thus, mechanisms for a rapid improvement of T2D after RYGB may occur mainly in other tissues than adipose.

  • 127.
    Katsogiannos, Petros
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Kamble, Prasad G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Wiklund, Urban
    Umea Univ, Radiat Sciences, BioMed Engn & Informat, Umea, Sweden.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Espes, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Hammar, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery2020Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 67, nr 2, s. 344-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).

    Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.

    Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.

    Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.

  • 128.
    Kullberg, Joel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Haenni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Freden, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Börnert, Peter
    Ahlström, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gastric bypass promotes more lipid mobilization than a similar weight loss induced by low-calorie diet2011Ingår i: Journal of Obesity, ISSN 2090-0708, E-ISSN 2090-0716, Vol. 2011, s. 959601-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background.

    Recently, we found large reductions in visceral and subcutaneous fat one month after gastric bypass (GBP), without any change in liver fat content.

    Purpose.

    Firstly to characterize weight loss-induced lipid mobilization after one month with preoperative low-calorie diet (LCD) and a subsequent month following GBP, and secondly, to discuss the observations with reference to our previous published findings after GBP intervention alone.

    Methods.

    15 morbidly obese women were studied prior to LCD, at GBP, and one month after GBP. Effects on metabolism were measured by magnetic resonance techniques and blood tests.

    Results.

    Body weight was similarly reduced after both months (mean: -8.0 kg, n = 13). Relative body fat changes were smaller after LCD than after GBP (-7.1 ± 3.6% versus -10 ± 3.2%, P = .029, n = 13). Liver fat fell during the LCD month (-41%, P = .001, n = 13) but was unaltered one month after GBP (+12%).

    Conclusion.

    Gastric bypass seems to cause a greater lipid mobilization than a comparable LCD-induced weight loss. One may speculate that GBP-altered gastrointestinal signalling sensitizes adipose tissue to lipolysis, promoting the changes observed.

  • 129.
    Lagerros, Ylva Trolle
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden; Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Hedberg, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Bodén, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset. Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Suicide, Self-harm, and Depression After Gastric Bypass Surgery: A Nationwide Cohort Study2017Ingår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 265, nr 2, s. 235-243Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP).

    SUMMARY OF BACKGROUND DATA: Concerns regarding severe adverse psychiatric outcomes after GBP have been raised.

    METHODS: This nationwide, longitudinal, self-matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self-harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery.

    RESULTS: A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12).

    CONCLUSIONS: The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP.

  • 130. Lagerros, Ylva Trolle
    et al.
    Brandt, Lena
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hedberg, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Boden, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Risk of Suicide, Self-Harm and Depression after Gastric Bypass2015Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, s. S127-S127Artikel i tidskrift (Övrigt vetenskapligt)
  • 131.
    Langerth, Ann
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sandblom, Gabriel
    Karlson, Britt-Mari
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Long-term risk for acute pancreatitis, cholangitis, and malignancy more than 15 years after endoscopic sphincterotomy: a population-based study2015Ingår i: Endoscopy, ISSN 0013-726X, E-ISSN 1438-8812, Vol. 47, nr 12, s. 1132-1136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and study aims: It has been suggested that endoscopic sphincterotomy predisposes a patient to cholangitis, pancreatitis, and carcinoma in the pancreaticobiliary tract in the long term. Previous studies have shown an increased risk for acute cholangitis and pancreatitis but not for carcinoma. The aim of this study was to analyze these risks by conducting a long-term follow-up study of patients who underwent treatment for gallstone disease, comparing patients who underwent endoscopic sphincterotomy with those who did not. Patients and methods: A cohort of 1113 Swedish patients who were treated with endoscopic sphincterotomy between 1977 and 1990 for common bile duct stones was compared with two age-and sex-matched control groups with a history of cholecystectomy or cholecystectomy and cholangiotomy. Results: Over a median follow-up of more than 15 years after endoscopic sphincterotomy, the hazard ratio for endoscopic sphincterotomy versus cholecystectomy was 5.5 (95 % confidence interval [CI] 3.5 - 8.4) for cholangitis and 4.9 (95 %CI 2.8 - 8.6) for pancreatitis. The hazard ratio for endoscopic sphincterotomy versus cholangiotomy was 1.7 (95 %CI 1.3 - 2.4) for cholangitis and 1.5 (95 %CI 1.0 - 2.4) for pancreatitis. There was no significant increase in risk for malignant diagnoses. Conclusion: Patients who underwent endoscopic sphincterotomy for choledocholithiasis had an increased risk for acute pancreatitis and cholangitis in the long term compared with those not treated with endoscopic sphincterotomy. There was no increase in risk for malignancy in the pancreaticobiliary tract.

  • 132.
    Laurell, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hansson, Lars-Erik
    Gunnarsson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Diagnostic pitfalls and accuracy of diagnosis in acute abdominal pain2006Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, nr 10, s. 1126-1131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To identify the differential diagnostic difficulties in acute abdominal pain at the emergency department and during hospitalization. Material and methods. Patients with abdominal pain lasting for up to 7 days were registered during 1997-2000 and re-evaluated one year after discharge (n=2851). Results. Diagnoses with low sensitivity at the emergency department but markedly increased sensitivity at discharge were non-specific abdominal pain with a sensitivity value at the emergency department of 0.43, appendicitis 0.80, gallstones 0.68, constipation 0.74 and peptic ulcer 0.26. Corresponding K-values were 0.48, 0.74, 0.84, 0.88 and 0.93, respectively. Malignancy, gynaecological complaints, dyspepsia, urinary tract infection and diverticulitis displayed fairly good concordance between the preliminary and discharge judgements, but the predictive diagnostic value was still low at discharge. Sensitivity values at discharge were 0.40, 0.75, 0.73, 0.77 and 0.83, respectively. Among 479 surgically treated patients, 104 initially received a diagnosis usually not requiring surgery and had a median delay until operation of 22 h (95% CI 30-50 h), compared with 8 h (12-18 h) for referrals. Conclusions. Non-specific abdominal pain is the main differential diagnostic problem in the emergency department also for diagnoses requiring surgery. Constipation is a diagnostic pitfall and when making this diagnosis a careful re-evaluation is necessary.

  • 133.
    Lilienberg, Elsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Dubbelboer, Ilse R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Karalli, Amar
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Axelsson, Rimma
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Brismar, Torkel B,
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Ebeling Barbier, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Norén, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Duraj, Frans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hedeland, Mikael
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, S-75189 Uppsala, Sweden..
    Bondesson, Ulf
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, S-75189 Uppsala, Sweden.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Stål, Per
    Karolinska Inst, Dept Internal Med Huddinge, Gastroenterol Unit, Stockholm, Sweden.; Karolinska Univ Hosp Huddinge, Dept Digest Dis, Stockholm, Sweden..
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    In vivo Drug Delivery Performance of Lipiodol-based Emulsion or Drug-eluting Beads in Patients with Hepatocellular Carcinoma2017Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 14, nr 2, s. 448-458Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol, and their short-term safety and anti-tumor effects were also evaluated. In this open, prospective, non-randomized multi-center study, LIPDOX (n=13) or DEBDOX (n=12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmax and AUC0-24 h for DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p <0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.

  • 134.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Edén Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, F. Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasoreactivity is rapidly improved in obese subjects after gastric bypass surgery2009Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 33, nr 12, s. 1390-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. We investigated vasoreactivity in conduit and resistance arteries in morbidly obese subjects, and the effect of weight loss after gastric bypass surgery. METHODS: A total of 19 obese subjects (body mass index (BMI): 43.8+/-3.1 kg m(-2), 75% female, mean age 41 years) were investigated before surgery and after 1 and 12 months of surgery. Nineteen non-obese controls matched for age and gender were examined. Vasoreactivity was evaluated by ultrasound to measure flow-mediated dilation (FMD, evaluating a conduit vessel) and pulse-wave analysis with terbutaline provocation (change in reflectance index (RI), evaluating resistance vessels). RESULTS: Before surgery, the obese showed a low change in RI (18+/-12 vs 37+/-15% in controls, P=0.0001), but not significantly regarding FMD (7.9+/-6.4 vs 8.9+/-5.4% in controls). Surgery resulted in a weight loss of 9% at 1 month and 30% at 1 year. Change in RI markedly improved to 36+/-12% at 1 month (P=0.0001 vs baseline) and further to 44+/-11% at 1 year (P=0.014 vs 1 month). FMD did not change significantly. Heart rate and brachial artery diameter were reduced, with no significant change in blood pressure. The improvement in resistance vessel vasodilation, estimated as change in RI, was not correlated to changes in weight or measures of glucose and lipid metabolism. CONCLUSIONS: Obese patients showed impaired vasoreactivity in resistance arteries that was normalized already 1 month after gastric bypass surgery. The basis for this remarkable outcome, not significantly related to changes in body weight and metabolic variables, remains to be clarified.

  • 135. Lindberg, Fredrik
    et al.