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  • 51.
    Elias, Khalid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bekhali, Zakaria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Changes in bowel habits and patient-scored symptoms after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch2018In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 14, no 2, p. 144-149Article in journal (Refereed)
    Abstract [en]

    Background: Bariatric procedures are increasingly being used, but data on bowel habits are scarce.

    Objectives: To assess changes in gastrointestinal function and patient-scored symptoms after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS).

    Setting: University hospital in Sweden.

    Methods: We recruited 268 adult patients (mean age of 42.5 yr, body mass index 44.8, 67.9% female) listed for RYGB and BPD/DS. Patients answered validated questionnaires prospectively concerning bowel function, the Fecal Incontinence Quality of Life Scale, and the 36-Item Short Form Health Survey before and after their operation.

    Results: Postoperatively, 208 patients (78.2% of 266 eligible patients) answered the questionnaires. RYGB patients had fewer bowel motions per week (8 versus 10) and more abdominal pain postoperatively (P<.001). Postoperatively, the 35 BPD/DS patients (69% versus 23%) needed to empty their bowel twice or more than twice daily, reported more flatus and urgency, and increased need for keeping a diet (P<.001). Concerning Fecal Incontinence Quality of Life Scale, coping and behavior was slightly reduced while depression and self-perception scores were improved after RYGB. Lifestyle, coping and behavior, and embarrassment were reduced after BPD/DS (P<.05). In the 36-Item Short Form Health Survey, physical scores were markedly improved, while mental scores were largely unaffected.

    Conclusion: RYGB resulted in a reduced number of bowel movements but increased problems with abdominal pain. In contrast, BPD/DS-patients reported higher frequency of bowel movements, more troubles with flatus and urgency, and increased need for keeping a diet. These symptoms affected quality of life negatively, however, general quality of life was markedly improved after both procedures. These results will be of great value for preoperative counseling.

  • 52.
    Engström, Björn E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Karlsson, F. Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 3, p. 476-480Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. DESIGN: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal). SUBJECTS: Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.9+/-3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7+/-5.8 kg/m(2)), 10 middle-aged non-obese (BMI 23.5+/-2.2 kg/m(2)) and 10 young non-obese (BMI 22.7+/-1.8 kg/m(2)). MEASUREMENTS: Ghrelin, glucose and insulin levels were analysed pre- and postprandially. RESULTS: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. CONCLUSION: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.

  • 53.
    Eriksson, Lars-Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ljungdahl, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Transcatheter arterial embolization versus surgery in the treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure2008In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 19, no 10, p. 1413-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To retrospectively compare the outcome of transcatheter arterial embolization (TAE) and surgery as salvage therapy of upper gastrointestinal bleeding after failed endoscopic treatment. MATERIALS AND METHODS: From January 1998 to December 2005, 658 patients were referred to diagnostic/therapeutic emergency endoscopy and diagnosed with upper gastrointestinal bleeding. Ninety-one of these 658 patients (14%) had repeat bleeding or continued to bleed. Forty of those 91 patients were treated with TAE and 51 were treated with surgery. From the medical records, the following variables were recorded: demographic data, endoscopic diagnoses, comorbidities, lowest hemoglobin levels, total transfusion requirements, lengths of hospitalization stays, postprocedure complications, and mortality rates. The relative survival rate was calculated, and survival probability was calculated with the Kaplan-Meier technique. RESULTS: Patients treated with TAE were older (mean age, 76 years; age range, 40-94 years) and had slightly more comorbidities compared to patients who underwent surgery (mean age, 71 years; age range, 45-89 years). The 30-day mortality rate in patients treated with TAE was one of 40 (3%) compared to seven of 51 (14%) in patients treated with surgery (P < .07). Most repeat bleeding could be effectively treated with TAE, both in the surgical and TAE groups. CONCLUSIONS: The results of this study suggest that, after failure of therapeutic endoscopy for upper gastrointestinal bleeding, TAE should be the treatment of choice before surgery and that TAE can also be used to effectively control bleeding after failed surgery or TAE. There was a clear trend to lower 30-day mortality with use of TAE instead of surgery.

  • 54.
    Eriksson, Lars-Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ljungdahl, Mikael
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nyman, Rickard
    Transcatheter arterial emoblization versus surgery for treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure.Manuscript (Other academic)
  • 55.
    Fors, Diddi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eiriksson, Kristinn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Arvidsson, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Elevated PEEP without effect upon gas embolism frequency or severity in experimental laparoscopic liver resection2012In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 109, no 2, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Carbon dioxide (CO2) embolism is a potential complication in laparoscopic liver surgery. Gas embolism (GE) is thought to occur when central venous pressure (CVP) is lower than the intra-abdominal pressure (IAP). This study aimed to investigate whether an increased CVP due to induction of PEEP could influence the frequency and severity of GE during laparoscopic liver resection. Twenty anaesthetized piglets underwent laparoscopic left liver lobe resection and were randomly assigned to either 5 or 15 cm H2O PEEP (n10 per group). During resection, a standardized injury to the left hepatic vein [venous cut (VC)] was created to increase the risk of GE. Haemodynamic and respiratory variables were monitored, and online arterial blood gas monitoring and transoesophageal echocardiography (TOE) were used. The occurrence and severity of embolism was graded as 0 (none), 1 (minor), or 2 (major), depending on the TOE results. No differences were found between the two groups regarding the frequency or severity of GE, during either the VC (P0.65) or the rest of the surgery (P0.24). GE occurred irrespective of the CVPIAP gradient. Mechanisms other than the CVPIAP gradient seemed during laparoscopic liver surgery to contribute to the formation of CO2 embolism. This is of clinical importance to the anaesthetists.

  • 56.
    Fors, Diddi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eiriksson, Kristinn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Waage, A.
    Arvidsson, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    High Frequency Jet Ventilation shortened the duration of gas embolisation during experimental laparoscopic liver resection Article in journal (Refereed)
  • 57.
    Frühling, Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Reply to: Microwave thermosphere (TM) ablation in the multimodal management of colorectal cancer liver metastasis2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 10, p. 1979-1979Article in journal (Other academic)
  • 58.
    Frühling, Petter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 4, p. 751-757Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 59.
    Gerdin, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Persson, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Classification, prioritization and distribution of responsibility. Cooperation of specialties for an optimal trauma care1996In: Läkartidningen, Vol. 93, p. 2656-Article in journal (Other academic)
  • 60.
    Gerdin, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Persson, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Specialistsamverkan vid optimal traumavård. Klassning, prioritering och ansvarsfödelning1996In: Läkartidningen, Vol. 93, p. 2656-Article in journal (Other academic)
  • 61.
    Gilg, Stefan
    et al.
    Karolinska Inst, Inst Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden; Karolinska Univ Hosp, Ctr Digest Dis, Dept Surg, Stockholm, Sweden.
    Sandström, Per
    Linköping Univ Hosp, Cty Council Östergötland, Dept Surg & Clin & Expt Med, Linköping, Sweden.
    Rizell, Magnus
    Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Lindell, Gert
    Skånes Univ Hosp, Lund, Sweden.
    Ardnor, Bjarne
    Norrlands Univ Hosp, Umeå, Sweden.
    Strömberg, Cecilia
    Karolinska Inst, Inst Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden; Karolinska Univ Hosp, Ctr Digest Dis, Dept Surg, Stockholm, Sweden.
    Isaksson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Karolinska Univ Hosp, Ctr Digest Dis, Dept Surg, Stockholm, Sweden.
    The impact of post-hepatectomy liver failure on mortality: a population-based study2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 10-11, p. 1335-1339Article in journal (Refereed)
    Abstract [en]

    Background: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers.

    Aim: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy.

    Method: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5.

    Results: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3.

    Conclusion: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.

  • 62.
    Gilg, Stefan
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Surg, Ctr Digest Dis, Stockholm, Sweden.
    Sparrelid, Ernesto
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Surg, Ctr Digest Dis, Stockholm, Sweden.
    Saraste, Lars
    Karolinska Univ Hosp, Dept Anesthesiol & Intens Care, Stockholm, Sweden.
    Nowak, Greg
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Transplantat Surg, Stockholm, Sweden.
    Wahlin, Staffan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Hepatol, Stockholm, Sweden.
    Stromberg, Cecilia
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Surg, Ctr Digest Dis, Stockholm, Sweden.
    Lundell, Lars
    Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Surg, Ctr Digest Dis, Stockholm, Sweden.
    Isaksson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14186 Stockholm, Sweden.
    The Molecular Adsorbent Recirculating System in Posthepatectomy Liver Failure: Results From a Prospective Phase I Study2018In: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 2, no 4, p. 445-454Article in journal (Refereed)
    Abstract [en]

    Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50: 50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5-7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60- and 90-day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60- and 90-day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial.

  • 63.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Umeå.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Beskow, Anna H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Björ, Ove
    Umeå Univ, Dept Radiat Sci, Umeå.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Henriksson, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Jonsson, Håkan
    Umeå Univ, Dept Radiat Sci, Umeå.
    Larsson, Chatarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ljuslinder, Ingrid
    Umeå Univ, Dept Radiat Sci, Umeå.
    Mindus, Stephanie
    Akad Sjukhuset, Lung & Allergy Clin, Uppsala.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sandin, Fredrik
    Uppsala Univ Hosp, RCC Uppsala Örebro, Uppsala.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Solna.
    Stenling, Roger
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundström, Christer Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Thellenberg Karlsson, Camilla
    Umeå Univ, Dept Radiat Sci, Umeå.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Bergh, Anders
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Palmqvist, Richard
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 64.
    Gustafson, Elisabet K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Elgue, Graciela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hughes, Robin D.
    Mitry, Ragai R.
    Sanchez, Javier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Dhawan, Anil
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    The Instant Blood-Mediated Inflammatory Reaction Characterized in Hepatocyte Transplantation2011In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 6, p. 632-638Article in journal (Refereed)
    Abstract [en]

    Background. Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. Methods. By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. Results. We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. Conclusion. Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.

  • 65.
    Gustafsson, Ulla Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Randomized clinical trial of local gentamicin-collagen treatment in advancement flap repair for anal fistula2006In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 93, no 10, p. 1202-1207Article in journal (Refereed)
    Abstract [en]

    Background: Endoanal advancement flap repair is widely used in sphincter-preserving surgery for anal fistula, but the high recurrence rate is a major problem. A possible cause of non-healing is local infection of the flap. The aim of this study was to evaluate whether local antibiotic treatment with gentamicin-collagen improves healing after endoanal advancement flap repair for anal fistula.

    Methods: Eighty-three patients (52 men and 31 women; mean age 47 (range 17-71) years) who had endoanal advancement flap repair for anal fistula between September 1998 and January 2004 were randomized to surgery with (42 patients) or without (41 patients) application of gentamicin-collagen beneath the flap. Patients were evaluated at 1-3 and 12 months after surgery for healing and/or recurrence.

    Results: The overall healing rate with no recurrence at 1 year after surgery was 57 per cent (47 of 83). Twenty-six of 42 patients randomized to gentamicin-collagen healed primarily compared with 21 of 41 patients randomized to surgery only. There were no overall differences in healing rate according to sex, previous fistula surgery, complexity of fistula, smoking habit or body mass index.

    Conclusion: Endoanal advancement flap repair for anal fistula has a fairly high primary recurrence rate. Healing was not significantly improved by local application of gentamicin-collagen.

  • 66.
    Gustavsson, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Westling, Agneta
    Laparoscopic adjustable gastric banding: complications and side effects responsible for the poor long-term outcome2002In: Seminars in Laparoscopic Surgery, ISSN 1071-5517, E-ISSN 1532-8694, Vol. 9, no 2, p. 115-124Article in journal (Refereed)
    Abstract [en]

    In a remarkably short time, Laparoscopic Adjustable Gastric Banding (LAGB) has become a common operation for morbid obesity in Europe and elsewhere. More than 70,000 such procedures have been performed in recent years. We used LAGB as a routine treatment for morbid obesity in 90 patients between 1994 and 1996. We agree with other authors that LAGB is the least invasive of all gastric restrictive procedures, resulting in a low perioperative mortality and morbidity. The weight loss appears to be similar to that obtained by vertical banded gastroplasty (VBG). However, our long-term follow-up studies, including endoscopic examinations, as well as recent data in the literature also indicate a number of significant problems with LAGB. Patient discomfort occurs frequently in the postoperative course. When questioned according to a standardized protocol 2 years after surgery, every other patient in our series admitted heartburn and acid regurgitation. Regular endoscopic surveillance revealed a prevalence of erosive esophagitis of 44%. After a median follow-up of 7 years, 58% of the patients had been reoperated on, almost always with excision of the banding system and conversion to Roux-en-Y gastric bypass (RYGBP). The reasons for reoperation were esophagitis, band erosion, pouch dilatation, leakage from the balloon, and esophageal dilatation, complications that also have been described in several recent papers in the literature. Our prediction is that LAGB will not stand the test of time.

  • 67.
    Haglund, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Frisk, Jessica
    Ivarsson, Marie-Louise
    Naredi, Peter
    Rydén, Lisa
    ST-utbildningen ska ge kompetens i medicinsk vetenskap: Kirurgföreningen föreslår en kursplan för alla ST-läkare2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 6, p. 369-72Article in journal (Refereed)
  • 68.
    Haglund, Ulf H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Urdzik, Jozef
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Right hemihepatectomy2008In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 12, no 7, p. 1283-1287Article in journal (Refereed)
    Abstract [en]

    A right hemihepatectomy is frequently required for surgical removal of colorectal liver metastases. Today, this procedure can be performed quite safely provided the remaining liver is free from significant disease including steatohepatitis due to prolonged cytostatic treatment. Standard surgical techniques for liver resection are described in surgical textbooks. However, each center has developed its own modifications of important details. In this paper, we describe our technique to resect the right liver lobe using conventional surgical techniques as well as a vascular stapler and an ultrasonic dissector. This technique has proven to be quite safe, and blood loss is most often not significant despite we do not routinely apply the Pringle's manoeuvre during the division of the liver parenchyma.

  • 69.
    Haglund, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Routine intraoperative cholangiography in elective laparoscopic cholecystectomy2010In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 99, no 4, p. 195-196Article in journal (Other academic)
  • 70.
    Haglund, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Appendix2017In: Kirurgi / [ed] Hamberger & Haglund, Liber, 2017, 9, p. 283-287Chapter in book (Refereed)
  • 71.
    Haglund, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tunntarmen2017In: Kir / [ed] Hamberger & Haglund, Liber, 2017, 9, p. 273-282Chapter in book (Refereed)
  • 72.
    Halim, Abdul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Degerblad, Marie
    Karolinska Institutet.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Juul Holst, Jens
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Glucagon-like peptide-1 inhibits prandial gastrointestinal motility through myenteric neuronal mechanisms in humans2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 2, p. 575-585Article in journal (Refereed)
    Abstract [en]

    Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility.

    Objective: Investigate whether physiological plasma concentrations of GLP-1 can inhibit human postprandial gastrointestinal motility; determine target mechanism of GLP-1 and analogue ROSE-010 action.

    Design: Single-blind parallel study.

    Setting: University research laboratory.

    Participants: Healthy volunteers investigated with antroduodenojejunal manometry. Human gastric, intestinal and colonic muscle strips.

    Interventions: Motility indices (MI) obtained before and during infusion of saline or GLP-1 were compared. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips, pre-contracted with bethanechol/electric field stimulation (EFS), investigated for GLP-1- or ROSE-010-induced relaxation. GLP-1, GLP-2 and their receptors localized by immunohistochemistry. Action mechanisms studied employing exendin(9-39)amide, Lω-nitro-monomethylarginine (L-NMMA), 2´,5´-dideoxyadenosine (DDA), tetrodotoxin (TTX).

    Main outcome measures: Hypothesize postprandial gastric relaxation induced by GLP-1, the mechanism of which intrinsic neuronally-mediated.

    Results: Food intake increased MI to 6.4±0.3 (antrum), 5.7±0.4 (duodenum) and 5.9±0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not GLP-2. GLP-1 0.7 pmol/kg·min significantly suppressed MI to 4.6±0.2, 4.7±0.4 and 5.0±0.2, respectively, while 1.2 pmol/kg·min suppressed corresponding MI to 5.4±0.2, 4.4±0.3 and 5.4±0.3 (p<0.0001-0.005). GLP-1 and ROSE-010 prevented bethanechol- or EFS-induced muscle contractions (p <0.005-0.05). Inhibitory responses to GLP-1 and ROSE-10 were blocked by exendin(9-39)amide, L-NMMA, DDA or TTX (all p <0.005-0.05). GLP-1 and GLP-2 were localized to epithelial cells; GLP-1 also in myenteric neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle, GLP-1R also in epithelial cells.

    Conclusions: GLP-1 inhibits postprandial motility through GLP-1R at myenteric neurons, involving nitrergic and cAMP-dependent mechanisms.

  • 73.
    Halim, M. Abdul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Gillberg, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Boghus, Sandy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellstrom, Per. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nitric oxide regulation of migrating motor complex: randomized trial of N-G-monomethyl-L-arginine effects in relation to muscarinic and serotonergic receptor blockade2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, no 2, p. 105-118Article in journal (Refereed)
    Abstract [en]

    Aim: The migrating motor complex (MMC) propels contents through the gastrointestinal tract during fasting. Nitric oxide (NO) is an inhibitory neurotransmitter in the gastrointestinal tract. Little is known about how NO regulates the MMC. In this study, the aim was to examine nitrergic inhibition of the MMC in man using N-G-monomethyl-L-arginine (L-NMMA) in combination with muscarinic receptor antagonist atropine and 5-HT3 receptor antagonist ondansetron. Methods: Twenty-six healthy volunteers underwent antroduodenojejunal manometry for 8 h with saline or NO synthase (NOS) inhibitor L-NMMA randomly injected I.V. at 4 h with or without atropine or ondansetron. Plasma ghrelin, motilin and somatostatin were measured by ELISA. Intestinal muscle strip contractions were investigated for NO-dependent mechanisms using L-NMMA and tetrodotoxin. NOS expression was localized by immunohistochemistry. Results: L-NMMA elicited premature duodenojejunal phase III in all subjects but one, irrespective of atropine or ondansetron. L-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. L-NMMA did not change circulating ghrelin, motilin or somatostatin. Intestinal contractions were stimulated by L-NMMA, insensitive to tetrodotoxin. NOS immunoreactivity was detected in the myenteric plexus but not in smooth muscle cells. Conclusion: Nitric oxide suppresses phase III of MMC independent of muscarinic and 5-HT3 receptors as shown by nitrergic blockade, and acts through a neurocrine disinhibition step resulting in stimulated phase III of MMC independent of cholinergic or 5-HT3-ergic mechanisms. Furthermore, phase II of MMC is governed by inhibitory nitrergic and excitatory cholinergic, but not 5-HT3-ergic mechanisms.

  • 74.
    Halim, Md Abdul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Gillberg, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Boghus, Sandy
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dominic-Luc, Webb
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    M. Hellström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nitric oxide regulation of migrating motor complex: randomised trial of L-NMMA effects in relation to muscarinic and serotonergic receptor blockade2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, no 2, p. 105-118Article in journal (Refereed)
    Abstract [en]

    Aim

    The migrating motor complex (MMC) propels contents through the gastrointestinal tract during fasting. Nitric oxide (NO) is an inhibitory neurotransmitter in the gastrointestinal tract. Little is known about how NO regulates the MMC. In this study, the aim was to examine nitrergic inhibition of the MMC in man using NG-monomethyl-l-arginine (l-NMMA) in combination with muscarinic receptor antagonist atropine and 5-HT3 receptor antagonist ondansetron.

    Methods

    Twenty-six healthy volunteers underwent antroduodenojejunal manometry for 8 h with saline or NO synthase (NOS) inhibitor l-NMMA randomly injected I.V. at 4 h with or without atropine or ondansetron. Plasma ghrelin, motilin and somatostatin were measured by ELISA. Intestinal muscle strip contractions were investigated for NO-dependent mechanisms using l-NMMA and tetrodotoxin. NOS expression was localized by immunohistochemistry.

    Results

    l-NMMA elicited premature duodenojejunal phase III in all subjects but one, irrespective of atropine or ondansetron. l-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. l-NMMA did not change circulating ghrelin, motilin or somatostatin. Intestinal contractions were stimulated byl-NMMA, insensitive to tetrodotoxin. NOS immunoreactivity was detected in the myenteric plexus but not in smooth muscle cells.

    Conclusion

    Nitric oxide suppresses phase III of MMC independent of muscarinic and 5-HT3 receptors as shown by nitrergic blockade, and acts through a neurocrine disinhibition step resulting in stimulated phase III of MMC independent of cholinergic or 5-HT3-ergic mechanisms. Furthermore, phase II of MMC is governed by inhibitory nitrergic and excitatory cholinergic, but not 5-HT3-ergic mechanisms.

  • 75.
    Halim, Md. Abdul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala University.
    Marie, Degerblad
    Karolinska Institutet.
    Dominic-Luc, Webb
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala University.
    Magnus, Sundbom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala University.
    Hellström, Per M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala University.
    GLP-1 Inhibits Prandial Antro-Duodeno-Jejunal Motility in Humans: Native GLP-1 Compared With Analogue ROSE-010 In Vitro2016In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 150, no 4, suppl. 1, p. S97-S98Article in journal (Refereed)
    Abstract [en]

    Background: Glucagon-like peptide-1 (GLP-1) is secreted from L-cells after nutrient ingestion, inhibiting motility. Aims: To clarify whether infused GLP-1 inhibits in vivo prandial motility response and determine the likeliest target cell type and mechanism of action of GLP-1 and its analogue ROSE-010 using in vitro human gut muscle strips. Methods: Sixteen healthy volunteers underwent antroduodenojejunal manometry. Recordings of 1 hour infusion of saline or GLP-1 (0.7 or 1.2 pmol/kg/min) were compared. Plasma GLP-1 and GLP-2 were measured by RIA. Gastrointestinal muscle strips from surgical re-sections, pre-contracted with bethanechol or electric field stimulation (EFS), were investigated for GLP-1 or ROSE-010 induced relaxation. GLP-1, GLP-2 and receptors for GLP-1 and GLP-2 (GLP-1R, GLP-2R) were visualized by immunohistochemistry. Mechanisms were studied employing exendin(9-39) amide, Lw-nitro-monomethyl arginine (L-NMMA), 2´5´-dideoxyadenosine (DDA) and tetrodotoxin (TTX). Results: Food-intake increased motility index from 4.0±0.5 to 6.4±0.3 (antrum), 4.2±0.4 to 5.7±0.4 (duodenum) and 4.6±0.3 to 5.9±0.2 (jejunum) ln(Σ(mmHg·s·min-1)). GLP-1 at 0.7 pmol/kg/minwas sufficient to suppress these indexes from 6.2±0.4 to 3.8±0.7, 5.6±0.6 to 3.9±0.6 and 5.8±0.1 to 4.6±0.4 ln(Σ(mmHg·s·min-1)). Both GLP-1 doses raised plasma GLP-1, but not GLP-2. GLP-1 (EC50 40 nM) and ROSE-010 (EC50 50 nM) relaxed bethanechol-induced contractions in muscle strips. Inhibitory responses were blocked by exendin(9-39) amide, L-NMMA, DDA or TTX pre-treatment. GLP-1R and GLP-2R were expressed in myenteric neurons, but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit motility through GLP-1R at myenteric neurons, which also possess GLP-2 receptors. GLP-1 increases more than GLP-2 with meals and does not increase plasma GLP-2. GLP-1 and ROSE-010 relaxations are cAMP and NO dependent.

  • 76.
    Hasselgren, Kristina
    et al.
    Linkoping Univ, Dept Surg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Sandstrom, Per
    Linkoping Univ, Dept Surg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Røsok, Bård Ingvald
    Oslo Univ Hosp, Dept Hepatopancreatobiliary Surg, Oslo, Norway.
    Sparrelid, Ernesto
    Karolinska Inst, Karolinska Univ Hosp, Div Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Lindell, Gert
    Skane Univ Hosp, Dept Surg, Lund, Sweden.
    Nørgaard Larsen, Peter
    Univ Copenhagen, Dept Surg Gastroenterol & Transplantat, Rigshosp, Copenhagen, Denmark.
    Larsson, Anna Lindhoff
    Linkoping Univ, Dept Surg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Schultz, Nicolai A.
    Univ Copenhagen, Dept Surg Gastroenterol & Transplantat, Rigshosp, Copenhagen, Denmark.
    Bjornbeth, Bjorn Atle
    Oslo Univ Hosp, Dept Hepatopancreatobiliary Surg, Oslo, Norway.
    Isaksson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rizell, Magnus
    Univ Gothenburg, Sahlgrenska Acad, Dept Transplantat & Liver Surg, Gothenburg, Sweden.
    Bjornsson, Bergthor
    Linkoping Univ, Dept Surg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO2019In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 23, no 3, p. 556-562Article in journal (Refereed)
    Abstract [en]

    Background Portal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.

    Methods Patients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.

    Results Forty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (±4), compared to 1.5 (±2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (±4) the first week, compared to 4.3 (±2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (±2), respectively (±0.1) (p=0.017).

    Discussion The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.

  • 77.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gastrointestinal Physiology and Results following Bariatric Surgery2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The number of operations for morbid obesity is rising fast. We have examined aspects of postoperative physiology and results after bariatric surgery.

    The pH in the proximal pouch after Roux-en-Y gastric bypass (RYGBP) was investigated with catheter-based and wire-less technique. Gastric emptying, PYY-levels in the fasting state and after a standardized meal was evaluated after biliopancreatic diversion with duodenal switch (DS). A clinical trial was undertaken, comparing DS to RYGBP in patients with BMI>48. Main outcome variables were safety and long-term weight results as well as abdominal symptoms and laboratory results.

    Patients with stomal ulcer had significantly lower pH in their proximal gastric pouch as compared to asymptomatic control subjects. Long-time pH measurements with the wire-less BRAVO-system were feasible and demonstrated pH<4 in median 10.5% of the time in asymptomatic post-RYGBP patients. After DS, the T50 of gastric emptying was 28±16 minutes. PYY-levels were higher after DS than in age-matched control subjects. BMI-reduction was greater after DS (24 BMI-units) than after RYGBP (17 BMI-units) in median 3.5 (2.0-5.3) years after surgery (p<0.001). Fasting glucose and HbA1c levels were lower one and three years after DS as compared to RYGBP. On the other hand, DS-patients reported having more diarrhea and malodorous flatus.

    This thesis has resulted in deepened knowledge. Acid produced in the proximal pouch is an important pathogenetic factor in the development of stomal ulcer after RYGBP. However, symptom-free patients have an acidic environment in the proximal Roux-limb as well. After DS, gastric emptying is fast, but not instantaneous, and PYY-levels are high. DS results in superior weight reduction and better glucose control as compared to RYGBP in patients with BMI>48. We believe that DS has a place in surgical treatment of the super-obese, even though symptoms of diarrhea and malodorous flatus are more common after DS.

     

    List of papers
    1. Role of gastric acid in stomal ulcer after gastric bypass.
    Open this publication in new window or tab >>Role of gastric acid in stomal ulcer after gastric bypass.
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    2005 (English)In: Obes Surg, ISSN 0960-8923, Vol. 15, no 10, p. 1375-8Article in journal (Refereed) Published
    Keywords
    Adult, Aged, Angiography/*methods, Artifacts, Balloon Dilatation, Contrast Media/administration & dosage, Female, Humans, Imaging; Three-Dimensional, Kidney Transplantation/radiography, Male, Middle Aged, Renal Artery/*radiography/*transplantation, Renal Artery Obstruction/*radiography, Reproducibility of Results, Research Support; Non-U.S. Gov't, Rotation
    Identifiers
    urn:nbn:se:uu:diva-75443 (URN)16354514 (PubMedID)
    Available from: 2006-06-29 Created: 2006-06-29 Last updated: 2011-01-11
    2. Wire-less pH-metry at the gastrojejunostomy after Roux-en-Y Gastric Bypass: a novel use of the BRAVO™-system
    Open this publication in new window or tab >>Wire-less pH-metry at the gastrojejunostomy after Roux-en-Y Gastric Bypass: a novel use of the BRAVO™-system
    2011 (English)In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 25, no 7, p. 2302-2307Article in journal (Refereed) Published
    Abstract [en]

    Background

    The number of gastric bypass operations being preformed is increasing rapidly due to good weight loss and alleviation of co-morbidities in combination with low mortality and morbidity. Stomal ulcers are, however, a clinical problem after gastric bypass, giving patients discomfort, risk of bleeding or even perforation. To measure the acidity in the proximal jejunum, we adopted the wire-less pH-metry (BRAVO-system) developed for evaluating reflux esophagitis.

    Methods

    25 patients (4 men, median age 44 years, BMI 29.3) who had undergone RYGBP 4 years earlier were recruited. Twenty-one asymptomatic, non-PPI users and in addition, four symtomatic patients (ongoing or stopped PPI-treatment) were studied. The wire-less BRAVO-capsule was positioned at the level of the gastrojejunal anastomosis under visual control with the endoscope. pH was registered for up to 48 hours. Time with pH<4 was calculated. Two patients were studied with two capsules.

    Results

    Of the 25 recruited patients capsule placement was successful in all but 2 patients, and in 3 patients a constant neutral environment was seen before a premature loss of signal, indicating early loss of position, thus 20 successful measurements were made. The mean time of registration was 25.7 hours (6.1-47.4, n=20). In the 16 asymtomatic patients, median percentage of time with pH<4 at the gastrojejunostomy was 10.6% (range 0.4 -37.7%). When dividing the registration time in day (08.00-22.00) and night (22.00-06.00), the median percentage of time with pH<4 was 8.4 and 6.3, respectively, (p=0.08). The two double measurements gave similar results indicating consistency. No complications occurred.

    Conclusion

    Wire-less pH-measurements in the proximal jejunum after gastric bypass are feasible and safe. The acidity was significant (10.5% of the registration time) even in asymptomatic patients with small gastric pouches. The described method could be useful in evaluation of epigastralgia after gastric bypass and in appraisal of PPI treatment of stomal ulcer.

     

    Keywords
    Gastric bypass, Stomal ulcer, Ulcer, pH-metry, Acid
    National Category
    Medical and Health Sciences
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-131886 (URN)10.1007/s00464-010-1553-5 (DOI)000291690100034 ()21298531 (PubMedID)
    Available from: 2010-10-09 Created: 2010-10-09 Last updated: 2017-12-12Bibliographically approved
    3. Gastric Emptying and Postprandial PYY Response After Biliopancreatic Diversion with Duodenal Switch
    Open this publication in new window or tab >>Gastric Emptying and Postprandial PYY Response After Biliopancreatic Diversion with Duodenal Switch
    Show others...
    2011 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 21, no 5, p. 609-615Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Super-obesity (BMI > 50) is increasing rapidly. We use the biliopancreatic diversion with duodenal switch (BPD-DS) as one option in this patient category. The aim of the present study was to investigate the emptying of the gastric tube, PYY levels and dumping symptoms after BPD-DS.

    METHODS: Emptying of the gastric tube was investigated with scintigraphy after an overnight fast. Twenty patients (median age 43 years, BMI 31.1 kg/m(2)) having undergone BPD-DS in median 3.5 years previously were included in the scintigraphic study. A technetium-labelled omelette was ingested and scintigraphic evaluation of gastric emptying was undertaken. Ten of the patients also underwent PYY measurements after a standardised meal and were compared to nine non-operated age-matched normal weight controls, both in the fasting state and after the test meal. Frequency of dumping symptoms was evaluated in all patients.

    RESULTS: The half-emptying time was 28 ± 16 min. Lag phase was present in 30% of the patients. PYY levels were significantly higher in BPD-DS patients as compared to controls both in the fasting state (p < 0.001) and after the test meal (p < 0.001). Dumping symptoms were scarce and occurred in 17 of the 20 patients only few times yearly or less.

    CONCLUSIONS: Although the pylorus is preserved in BPD-DS, the stomach emptying is faster than in non-operated subjects. PYY levels are elevated in the fasting state after BPD-DS and a marked response to a test meal is seen, likely due to the rapid stimulation of intraluminal nutrients in the distal ileum. In spite of this, dumping symptoms are uncommon.

    Keywords
    Duodenal switch, Gastric emptying, PYY, Scintigraphy, Morbid obesity, Dumping
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-131876 (URN)10.1007/s11695-010-0288-7 (DOI)000289114300011 ()20862615 (PubMedID)
    Available from: 2010-10-08 Created: 2010-10-08 Last updated: 2017-12-12Bibliographically approved
    4. Superior weight loss and lower HbA1c 3 years after duodenal switch compared with Roux-en-Y gastric bypass: a randomized controlled trial
    Open this publication in new window or tab >>Superior weight loss and lower HbA1c 3 years after duodenal switch compared with Roux-en-Y gastric bypass: a randomized controlled trial
    2012 (English)In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 8, no 3, p. 338-343Article in journal (Refereed) Published
    Abstract [en]

    Background: Obesity is a rising threat to public health. The relative increase in the incidence of morbid obesity is most pronounced in the most severely obese. Roux-en-Y gastric bypass (RYGB) results in inferior weight loss in this group. Therefore, we have offered biliopancreatic diversion with duodenal switch (BPD/DS) as an alternative for this patient category. Our objective was to compare BPD/DS and RYGB in the surgical treatment of morbid obesity in patients with a body mass index (BMI) >48 kg/m(2). The setting was a university hospital in Sweden.

    Methods: In a controlled trial (registration number 1SRCTN10940791), 47 patients (25 men, BMI 54.5 +/- 6.1 kg/m(2)) were randomized to RYGB (n = 23) or BPD/DS (n = 24). Biochemical data were collected preoperatively and 1 and 3 years postoperatively. A questionnaire addressing weight, general satisfaction, and gastrointestinal symptoms was distributed a median of 4 years postoperatively.

    Results: Both procedures were safe. The duration of surgery and postoperative morphine consumption were greater after BPD/DS than after RYGB (157 versus 117 min and 140 versus 93 mg, respectively). BPD/DS resulted in greater weight loss than RYGB (-23.2 +/- 4.9 versus 16.2 +/- 6.9 BMI units or 80% +/- 15% versus 51% +/- 23% excess BMI loss, P < .001). BPD/DS yielded lower glucose and glycated hemoglobin levels at 3 years. More patients listed troublesome diarrhea and malodorous flatus in the questionnaire after BPD/DS, but no significant difference was seen (P = .078 and P = .073, respectively).

    Conclusions: BPD/DS produced superior weight results and lower glycated hemoglobin levels compared with RYGB in patients with a BMI >48 kg/m(2). Both operations yield high satisfaction rates. However, diarrhea tended to be more common after BPD/DS.

    Keywords
    Duodenal switch, Roux-en-Y gastric bypass, Weight loss, Abdominal symptoms, Glucose control
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-131888 (URN)10.1016/j.soard.2012.01.014 (DOI)000304520900015 ()
    Note
    Manuscript title: Superior weight loss and glucose control three years after duodenal switch compared to Roux-en-Y gastric bypassAvailable from: 2010-10-09 Created: 2010-10-09 Last updated: 2017-12-12Bibliographically approved
  • 78.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gustavsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Long-term follow-up in patients undergoing open gastric bypass as a revisional operation for previous failed restrictive procedures2012In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 8, no 6, p. 696-701Article in journal (Refereed)
    Abstract [en]

    Background

    We have previously described our early experience with Roux-en-Y gastric bypass (RYGB) as a revisional procedure. The favorable results have stimulated us to continue using RYGB as our standard operating procedure after failed bariatric surgery. Our objective was to evaluate the perioperative risks, weight result, and abdominal symptoms 5 years after revisional RYGB surgery at a university hospital in Sweden.

    Methods

    We studied 121 patients undergoing revisional open RYGB (age 42.0 yr, body mass index 37.7 kg/m2, 101 women) 5 years after RYGB surgery. The patients underwent reoperation because of either intolerable side effects or inferior weight loss. The initial procedures were horizontal gastroplasty (n = 2), vertical banded gastroplasty (n = 34), gastric banding (n = 21), and silicone adjustable gastric banding (n = 64). The mean interval between the first surgery and revision was 5 years. The 5-year follow-up data were obtained annually using a questionnaire survey.

    Results

    The average operating time was 162 minutes (range 75–355). In these 121 cases, 10 (8%) reoperations were performed in the first 30-day period (4 for leakage). No perioperative mortality occurred, and the 5-year follow-up rate was 91%. The mean body mass index was 30.7 kg/m2. Seven patients (5.7%) had undergone subsequent surgery because of complications. At follow-up, 93% reported being very satisfied or satisfied with the revisional procedure. Disturbing abdominal symptoms after RYGB were rare.

    Conclusion

    The perioperative risks of revisional RYGB are greater than those for primary RYGB. However, because the long-term weight results and patient satisfaction are very good, we believe that the 8% reoperative rate is acceptable. We consider RYGB to be a suitable procedure for patients in whom previous bariatric procedures have failed.

  • 79.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Karlsson, F. Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Edén-Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gastric Emptying and Postprandial PYY Response After Biliopancreatic Diversion with Duodenal Switch2011In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 21, no 5, p. 609-615Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Super-obesity (BMI > 50) is increasing rapidly. We use the biliopancreatic diversion with duodenal switch (BPD-DS) as one option in this patient category. The aim of the present study was to investigate the emptying of the gastric tube, PYY levels and dumping symptoms after BPD-DS.

    METHODS: Emptying of the gastric tube was investigated with scintigraphy after an overnight fast. Twenty patients (median age 43 years, BMI 31.1 kg/m(2)) having undergone BPD-DS in median 3.5 years previously were included in the scintigraphic study. A technetium-labelled omelette was ingested and scintigraphic evaluation of gastric emptying was undertaken. Ten of the patients also underwent PYY measurements after a standardised meal and were compared to nine non-operated age-matched normal weight controls, both in the fasting state and after the test meal. Frequency of dumping symptoms was evaluated in all patients.

    RESULTS: The half-emptying time was 28 ± 16 min. Lag phase was present in 30% of the patients. PYY levels were significantly higher in BPD-DS patients as compared to controls both in the fasting state (p < 0.001) and after the test meal (p < 0.001). Dumping symptoms were scarce and occurred in 17 of the 20 patients only few times yearly or less.

    CONCLUSIONS: Although the pylorus is preserved in BPD-DS, the stomach emptying is faster than in non-operated subjects. PYY levels are elevated in the fasting state after BPD-DS and a marked response to a test meal is seen, likely due to the rapid stimulation of intraluminal nutrients in the distal ileum. In spite of this, dumping symptoms are uncommon.

  • 80.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wire-less pH-metry at the gastrojejunostomy after Roux-en-Y Gastric Bypass: a novel use of the BRAVO™-system2011In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 25, no 7, p. 2302-2307Article in journal (Refereed)
    Abstract [en]

    Background

    The number of gastric bypass operations being preformed is increasing rapidly due to good weight loss and alleviation of co-morbidities in combination with low mortality and morbidity. Stomal ulcers are, however, a clinical problem after gastric bypass, giving patients discomfort, risk of bleeding or even perforation. To measure the acidity in the proximal jejunum, we adopted the wire-less pH-metry (BRAVO-system) developed for evaluating reflux esophagitis.

    Methods

    25 patients (4 men, median age 44 years, BMI 29.3) who had undergone RYGBP 4 years earlier were recruited. Twenty-one asymptomatic, non-PPI users and in addition, four symtomatic patients (ongoing or stopped PPI-treatment) were studied. The wire-less BRAVO-capsule was positioned at the level of the gastrojejunal anastomosis under visual control with the endoscope. pH was registered for up to 48 hours. Time with pH<4 was calculated. Two patients were studied with two capsules.

    Results

    Of the 25 recruited patients capsule placement was successful in all but 2 patients, and in 3 patients a constant neutral environment was seen before a premature loss of signal, indicating early loss of position, thus 20 successful measurements were made. The mean time of registration was 25.7 hours (6.1-47.4, n=20). In the 16 asymtomatic patients, median percentage of time with pH<4 at the gastrojejunostomy was 10.6% (range 0.4 -37.7%). When dividing the registration time in day (08.00-22.00) and night (22.00-06.00), the median percentage of time with pH<4 was 8.4 and 6.3, respectively, (p=0.08). The two double measurements gave similar results indicating consistency. No complications occurred.

    Conclusion

    Wire-less pH-measurements in the proximal jejunum after gastric bypass are feasible and safe. The acidity was significant (10.5% of the registration time) even in asymptomatic patients with small gastric pouches. The described method could be useful in evaluation of epigastralgia after gastric bypass and in appraisal of PPI treatment of stomal ulcer.

     

  • 81.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hänni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Increased plasma magnesium concentrations 3 years after biliopancreatic diversion with duodenal switch2012In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 22, no 11, p. 1708-1713Article in journal (Refereed)
    Abstract [en]

    Background Biliopancreatic diversion with duodenal switch, BPD-DS, is a surgical procedure for treatment of super obese patients. It renders very good weight results and it strongly reduces the incidence of type 2 diabetes. One important mechanism of weight reduction after BPD-DS is malabsorption. Hypomagnesemia is an established cardiovascular risk factor. While it is wellknown that magnesium levels decline after jejuno-ileal bypass and increase after gastric bypass surgery, information on how magnesium status is affected by BPDDS is scant. The aim of the present study was to evaluate plasma magnesium concentrations (P-Mg) after BPD-DS. Methods Thirty-one patients, all Caucasians (9 diabetics, 12 men, age 38±8 years, weight 159±22 kg, body mass index (BMI) 53.9±5.2 kg/m 2) underwent BPD-DS. We evaluated weight, glycated hemoglobin levels (HbA1c) and P-Mg preoperatively as well as at 1 and 3 years after surgery. All subjects were treated with vitamin and mineral substitution after surgery, including 100 mg of magnesium salt. P-Mg was analyzed with respect to changes over time, correlation to BMI and HbA1c levels before and 3 years after surgery. Results The plasma magnesium concentrations increased by 15 % from 0.77±0.07 to 0.88±0.09 mmol/l over 3 years (p &lt;0.001). The weight loss was 71±25 kg. No patient had diabetes at follow-up. No correlations between P-Mg and BMI or HbA1c were seen. Conclusions Although exerting much of its weightreducing effect by a malabsorptive mechanism, BPD-DS yields a rise in P-Mg 3 years postoperatively, possibly contributing to the improved metabolic state after this operation.

  • 82.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Reply to Gastric Emptying After Sleeve Gastrectomy (OBSU-D-11-00201)2011In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 21, no 11, p. 1812-1813Article in journal (Refereed)
  • 83.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Superior weight loss and lower HbA1c 3 years after duodenal switch compared with Roux-en-Y gastric bypass: a randomized controlled trial2012In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 8, no 3, p. 338-343Article in journal (Refereed)
    Abstract [en]

    Background: Obesity is a rising threat to public health. The relative increase in the incidence of morbid obesity is most pronounced in the most severely obese. Roux-en-Y gastric bypass (RYGB) results in inferior weight loss in this group. Therefore, we have offered biliopancreatic diversion with duodenal switch (BPD/DS) as an alternative for this patient category. Our objective was to compare BPD/DS and RYGB in the surgical treatment of morbid obesity in patients with a body mass index (BMI) >48 kg/m(2). The setting was a university hospital in Sweden.

    Methods: In a controlled trial (registration number 1SRCTN10940791), 47 patients (25 men, BMI 54.5 +/- 6.1 kg/m(2)) were randomized to RYGB (n = 23) or BPD/DS (n = 24). Biochemical data were collected preoperatively and 1 and 3 years postoperatively. A questionnaire addressing weight, general satisfaction, and gastrointestinal symptoms was distributed a median of 4 years postoperatively.

    Results: Both procedures were safe. The duration of surgery and postoperative morphine consumption were greater after BPD/DS than after RYGB (157 versus 117 min and 140 versus 93 mg, respectively). BPD/DS resulted in greater weight loss than RYGB (-23.2 +/- 4.9 versus 16.2 +/- 6.9 BMI units or 80% +/- 15% versus 51% +/- 23% excess BMI loss, P < .001). BPD/DS yielded lower glucose and glycated hemoglobin levels at 3 years. More patients listed troublesome diarrhea and malodorous flatus in the questionnaire after BPD/DS, but no significant difference was seen (P = .078 and P = .073, respectively).

    Conclusions: BPD/DS produced superior weight results and lower glycated hemoglobin levels compared with RYGB in patients with a BMI >48 kg/m(2). Both operations yield high satisfaction rates. However, diarrhea tended to be more common after BPD/DS.

  • 84.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Duodenal switch versus Roux-en-Y gastric bypass for morbid obesity: systematic review and meta-analysis of weight results, diabetes resolution and early complications in single-centre comparisons2014In: Obesity Reviews, ISSN 1467-7881, E-ISSN 1467-789X, Vol. 15, no 7, p. 555-563Article in journal (Refereed)
    Abstract [en]

    Long-term weight loss after Roux-en-Y gastric bypass (RYGB) in super-obese patients has not been ideal. Biliopancreatic diversion with duodenal switch (DS) is argued to be better; however, additional side effects are feared. The aim of the present study was to determine differences in results after DS and RYGB in publications from single-centre comparisons. A systematic review of studies containing DS and RYGB performed at the same centre was performed. Outcome data were weight results, resolution of comorbid conditions, perioperative results and complications. Main outcome was difference in weight loss after DS and RYGB. Secondary outcomes were difference in resolution of comorbidities, perioperative results and complications. The final analysis included 16 studies with in total 874 DS and 1,149 RYGB operations. When comparing weight results at the longest follow-up of each study, DS yielded 6.2 (95% confidence interval 5.0-7.5) body mass index units additional weight loss compared with RYGB, P < 0.001. Operative time and length of stay were significantly longer after DS, as well as the risk for post-operative leaks, P < 0.05. DS is more effective than RYGB as a weight-reducing procedure. However, this comes at the price of more early complications and might also yield slightly higher perioperative mortality.

  • 85.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thuresson, M.
    Aarskog, P.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bodegard, J.
    Low-dose acetylsalicylic acid and gastrointestinal ulcers or bleeding - a cohort study of the effects of proton pump inhibitor use patterns2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 4, p. 371-380Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA). Design and setting A nationwide cohort study in Sweden. Patients All Swedish residents 40years of age, without cancer and receiving LDA treatment (80% adherence for 365days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as >60 of 90days covered by daily PPI doses and further divided into high (80%) or moderate (<80) adherence. All other PPI use was defined as intermittent use. Main outcome measures The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of >45days of LDA treatment interruption. Results During a median follow-up of 2.5years, 7880 of 648807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence. Conclusions In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.

  • 86.
    Hedberg, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Zacharias, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Janson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Preoperative Slow-Release Morphine Reduces Need of Postoperative Analgesics and Shortens Hospital Stay in Laparoscopic Gastric Bypass2016In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 26, no 4, p. 757-761Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As most bariatric procedures are performed by laparoscopy, hospital stay is exceptionally short, despite the habitus of patients and the rather extensive intra-abdominal surgery. To facilitate postoperative mobilization, most patients are given repeated single doses of morphine, a drug with several side effects. We aimed to evaluate the effect of preoperative treatment with a tablet of slow-release morphine (SRM) on postoperative analgesic consumption and length of stay (LOS) in laparoscopic gastric bypass (LGBP).

    METHODS: The SRM group (244 patients) was retrospectively compared to a control group (197 patients) concerning postoperative pain management and hospital stay by studying medical charts and data from Scandinavian Obesity Surgery Registry (SOReg).

    RESULTS: Patients in the SRM group needed significantly less analgesics during days 0, 1, and 2 postoperatively, morphine 10.7 vs. 13.6 mg, 10.2 vs. 13.9 mg, and 1.1 vs. 3.6 mg, respectively, p < 0.05, as well as acetaminophen, p < 0.05. According to a subgroup analysis, 20 mg of SRM was needed to obtain these effects. In addition, SRM patients had shorter hospital stay (2.3 vs. 3.5 days, p < 0.05) than the control group. No negative side effects were seen.

    CONCLUSIONS: Preoperatively administered slow-release morphine significantly reduced the need for postoperative analgesics and shortened hospital stay, without side effects or other complications. At our department, the studied regime is now routinely used in all bariatric surgery and we have started to use the concept in other groups of surgical patients.

  • 87.
    Hedenbro, J. L.
    et al.
    Lund Univ, Dept Surg, Lund, Sweden.;Aleris Obes Sweden, Lund, Sweden..
    Naslund, E.
    Danderyd Hosp, Dept Surg, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Boman, L.
    Lycksele Gen Hosp, Dept Surg, Lycksele, Sweden..
    Lundegayenrdh, G.
    Simrishamn Hosp, Dept Surg, Simrishamn, Sweden..
    Bylund, A.
    Ersta Diakoni, Dept Surg, Stockholm, Sweden..
    Ekelund, M.
    Lund Univ, Dept Surg, Lund, Sweden..
    Laurenius, A.
    Sahlgrens Acad, Dept Surg, Gothenburg, Sweden..
    Moller, P.
    Reg Hosp, Kalmar, Sweden..
    Olbers, T.
    Sahlgrens Acad, Dept Surg, Gothenburg, Sweden..
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ottosson, J.
    Univ Orebro, Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden..
    Naslund, I.
    Univ Orebro, Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden..
    Formation of the Scandinavian Obesity Surgery Registry, SOReg2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 10, p. 1893-1900Article in journal (Refereed)
    Abstract [en]

    Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that > 98 % of data are correct. All results are publicized annually on the Internet. Using this systematic approach, it has been possible to cover > 99 % of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.

  • 88.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Victor C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Patients Lacking Sustainable Long-Term Weight Loss after Gastric Bypass Surgery Show Signs of Decreased Inhibitory Control of Prepotent Responses2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0119896Article in journal (Refereed)
    Abstract [en]