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  • 251.
    Rönnblom, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Holmström, Tommy
    Dept Internal Med, Mariehamn, Aland, Finland..
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Tanghöj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Thörn, Mari
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjöberg, Daniel
    Falun Cent Hosp, Dept Internal Med, Falun, Sweden..
    Clinical course of Crohn's disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005-20092017Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 1, s. 81-86Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis. Material and Methods: Patients diagnosed with Crohn's disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005-2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death. Results: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death. Conclusions: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn's disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.

  • 252.
    Rönnblom, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Holmström, Tommy
    Dept Internal Med, Mariehamn, Finland..
    Tanghöj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Thörn, Mari
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjöberg, Daniel
    Falun Cent Hosp, Dept Internal Med, Falun, Sweden..
    Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009*2016Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, nr 11, s. 1339-1344Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality.

    Material and methods: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death.

    Results: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients<17 years at diagnosis, colectomy was performed in two (4.8%).

    Conclusions: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.

  • 253.
    Sakari, Thorbjörn B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Sjödahl, R.
    Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden..
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Role of icodextrin in the prevention of small bowel obstruction. Safety randomized patients control of the first 300 in the ADEPT trial2016Inngår i: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 18, nr 3, s. 295-300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AimAdhesions are the most common cause of small bowel obstruction (SBO). The costs of hospitalization and surgery for SBO are substantial for the health-care system. The adhesion-limiting potential of icodextrin has been shown in patients undergoing surgery for gynaecological diseases. A randomized, multicentre trial in colorectal cancer surgery started in 2009 with the aim of evaluating whether icodextrin could reduce the long-term risk of surgery for SBO. Because of some concerns about complications (especially anastomotic leakage) after icodextrin use, a preplanned interim analysis of morbidity and mortality was conducted. MethodPatients with colorectal cancer without metastasis were randomized 1:1 to receive standard surgery, with or without instillation of icodextrin in the abdominal cavity. For the first 300 patients, the 30-day follow-up data were collected from the Swedish ColoRectal Cancer Registry (SCRCR). Pre-, per- and postoperative data, morbidity and mortality were analysed. ResultsOf the 300 randomized patients, 288 had a data file in the SCRCR. Twelve patients did not have cancer and another five did not have a resection, leaving 283 for analysis. The authors were blinded to the randomization groups. Demographic data were similar in both groups. The overall complication rate was 24% in Group 1 and 23% in Group 2 (P=0.89). Four cases of anastomotic leakage were reported in Group 1 and five were reported in Group 2 (P=1.0). Mortality, intensive care unit (ICU) stay and re-operations did not differ between the groups. ConclusionThe pre-planned safety analysis of the first 300 patients enrolled in this randomized trial did not show any differences in adverse effects related to the use of icodextrin. All data were gathered from the SCRCR, giving us a strong message that we can continue to include patients in the trial.

  • 254.
    Schultz, J. K.
    et al.
    Akershus Univ Hosp, Dept Gastrointestinal Surg, PB 1000, N-1478 Lorenskog, Norway.;Univ Oslo, Inst Clin Med, Campus Ahus, Oslo, Norway..
    Wallon, C.
    Linkoping Univ, Dept Surg, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Blecic, L.
    Ostfold Hosp Kalnes, Dept Gastrointestinal Surg, Fredrikstad, Norway..
    Forsmo, H. M.
    Haukeland Hosp, Dept Gastrointestinal & Emergency Surg, Bergen, Norway.;Univ Bergen, Dept Clin Med, Bergen, Norway..
    Folkesson, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Buchwald, P.
    Skane Univ Hosp Malmo, Dept Surg, Colorectal Unit, Malmo, Sweden..
    Korner, H.
    Univ Bergen, Dept Clin Med, Bergen, Norway.;Stavanger Univ Hosp, Dept Gastrointestinal Surg, Stavanger, Norway..
    Dahl, F. A.
    Akershus Univ Hosp, Hlth Serv Res Ctr, Lorenskog, Norway.;Univ Oslo, Inst Clin Med, Campus Ahus, Oslo, Norway..
    Oresland, T.
    Akershus Univ Hosp, Dept Gastrointestinal Surg, PB 1000, N-1478 Lorenskog, Norway.;Univ Oslo, Inst Clin Med, Campus Ahus, Oslo, Norway..
    Yaqub, S.
    Oslo Univ Hosp, Dept Gastrointestinal Surg, Oslo, Norway..
    One-year results of the SCANDIV randomized clinical trial of laparoscopic lavage versus primary resection for acute perforated diverticulitis2017Inngår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, nr 10, s. 1382-1392Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Recent randomized trials demonstrated that laparoscopic lavage compared with resection for Hinchey III perforated diverticulitis was associated with similar mortality, less stoma formation but a higher rate of early reintervention. The aim of this study was to compare 1-year outcomes in patients who participated in the randomized Scandinavian Diverticulitis (SCANDIV) trial. Methods: Between February 2010 and June 2014, patients from 21 hospitals in Norway and Sweden presenting with suspected perforated diverticulitis were enrolled in a multicentre RCT comparing laparoscopic lavage and sigmoid resection. All patients with perforated diverticulitis confirmed during surgery were included in a modified intention-to-treat analysis of 1-year results. Results: Of 199 enrolled patients, 101 were assigned randomly to laparoscopic lavage and 98 to colonic resection. Perforated diverticulitis was confirmed at the time of surgery in 89 and 83 patients respectively. Within 1 year after surgery, neither severe complications (34 versus 27 per cent; P = 0.323) nor disease-related mortality (12 versus 11 per cent) differed significantly between the lavage and surgery groups. Among the 144 patients with purulent peritonitis, the rate of severe complications (27 per cent (20 of 74) versus 21 per cent (15 of 70) respectively; P = 0.445) and disease-related mortality (8 versus 9 per cent) were similar. Laparoscopic lavage was associated with more deep surgical-site infections (32 versus 13 per cent; P = 0.006) but fewer superficial surgical-site infections (1 versus 17 per cent; P = 0.001). More patients in the lavage group underwent unplanned reoperations (27 versus 10 per cent; P = 0.010). Including stoma reversals, a similar proportion of patients required a secondary operation (28 versus 29 per cent). The stoma rate at 1 year was lower in the lavage group (14 versus 42 per cent in the resection group; P < 0.001); however, the Cleveland Global Quality of Life score did not differ between groups. Conclusion: The advantages of laparoscopic lavage should be weighed against the risk of secondary intervention (if sepsis is unresolved). Assessment to excludemalignancy (although uncommon) is advised.

  • 255. Schultz, Johannes Kurt
    et al.
    Yaqub, Sheraz
    Wallon, Conny
    Blecic, Ljiljana
    Forsmo, Håvard Mjørud
    Folkesson, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Buchwald, Pamela
    Körner, Hartwig
    Dahl, Fredrik A
    Øresland, Tom
    chabok, abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: The SCANDIV Randomized Clinical Trial2015Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, nr 13, s. 1364-1375Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE: Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures.

    OBJECTIVE: To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis.

    DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled.

    INTERVENTIONS: Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered.

    MAIN OUTCOMES AND MEASURES: The primary outcome was severe postoperative complications (Clavien-Dindo score >IIIa) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life.

    RESULTS: The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage.

    CONCLUSIONS AND RELEVANCE: Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01047462.

  • 256. Schölin, Johnna
    et al.
    Buunen, Mark
    Hop, Wim
    Bonjer, Jaap
    Anderberg, Bo
    Cuesta, Miguel
    Delgado, Salvadora
    Ibarzabal, Ainitze
    Ivarsson, Marie-Louise
    Janson, Martin
    Lacy, Antonio
    Lange, Johan
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Skullman, Stefan
    Haglind, Eva
    Bowel obstruction after laparoscopic and open colon resection for cancer: results of 5 years of follow-up in a randomized trial2011Inngår i: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 25, nr 12, s. 3755-3760Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Postoperative bowel obstruction caused by intra-abdominal adhesions occurs after all types of abdominal surgery. It has been suggested that the laparoscopic technique should reduce the risk for adhesion formation and thus for postoperative bowel obstruction. This study was designed to compare the incidence of bowel obstruction in a randomized trial where laparoscopic and open resection for colon cancer was compared.

    METHODS: A retrospective analysis was performed, collecting data of episodes of bowel obstruction with or without surgery. Only episodes treated in the hospital where the index surgery took place were included. Data for 786 patients were collected for the 5-year period after cancer surgery.

    RESULTS: Baseline characteristics for the evaluated laparoscopic (n = 383) and open (n = 403) groups were comparable. The cumulative obstruction percentages at 5 years for the open and laparoscopic groups were 6.5 and 5.1% respectively and did not significantly differ from each other. Tumor stage seemed to influence the risk for bowel obstruction: 2.8% in stage I, 6.6% in stage II, and 7% in stage III, but the differences were not significant.

    CONCLUSIONS: This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.

  • 257. Segelman, J.
    et al.
    Granath, F.
    Holm, T.
    Machado, M.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Martling, A.
    Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer2012Inngår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, nr 5, s. 699-705Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: This was a population-based cohort study to determine the incidence, prevalence and risk factors for peritoneal carcinomatosis (PC) from colorectal cancer.

    Methods: Prospectively collected data were obtained from the Regional Quality Registry. The Cox proportional hazards regression model was used for multivariable analysis of clinicopathological factors to determine independent predictors of PC.

    Results: All 11 124 patients with colorectal cancer in Stockholm County during 1995-2007 were included and followed until 2010. In total, 924 patients (8.3 per cent) had synchronous or metachronous PC. PC was the first and only localization of metastases in 535 patients (4.8 per cent). The prevalence of synchronous PC was 4.3 per cent (477 of 11 124). The cumulative incidence of metachronous PC was 4.2 per cent (447 of 10 646). Independent predictors for metachronous PC were colonic cancer (hazard ratio (HR) 1.77, 95 per cent confidence interval 1.31 to 2.39; P = 0.002 for right-sided colonic cancer), advanced tumour (T) status (HR 9.98, 3.10 to 32.11; P < 0.001 for T4), advanced node (N) status (HR 7.41, 4.78 to 11.51; P < 0.001 for N2 with fewer than 12 lymph nodes examined), emergency surgery (HR 2.11, 1.66 to 2.69; P < 0.001) and non-radical resection of the primary tumour (HR 2.75, 2.10 to 3.61; P < 0.001 for R2 resection). Patients aged > 70 years had a decreased risk of metachronous PC (HR 0.69, 0.55 to 0.87; P = 0.003).

    Conclusion: PC is common in patients with colorectal cancer and is associated with identifiable risk factors.

  • 258. Siegel, R.
    et al.
    Cuesta, M. A.
    Targarona, E.
    Bader, F. G.
    Morino, M.
    Corcelles, R.
    Lacy, A. M.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Haglind, E.
    Bujko, K.
    Bruch, H. P.
    Heiss, M. M.
    Eikermann, M.
    Neugebauer, E. A. M.
    Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)2011Inngår i: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 25, nr 8, s. 2423-2440Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline.

    METHODS:

    An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference.

    RESULTS:

    Laparoscopic surgery for extraperitoneal (mid- and low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not inferior to the open in terms of disease-free survival, overall survival or local recurrence. Laparoscopic pelvic dissection may impair genitourinary and sexual function after rectal resection, like in open surgery.

    CONCLUSIONS:

    Laparoscopic surgery for mid- and low-rectal cancer can be recommended under optimal conditions. Still, most level 1 evidence is for colon cancer surgery rather than rectal cancer. Upcoming results from large randomised trials are awaited to strengthen the evidence for improved short-term results and equal long-term results in comparison with the open approach.

  • 259.
    Siilin, Helene
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Rastad, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ljunggren, Osten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lundgren, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Disturbances of calcium homeostasis consistent with mild primary hyperparathyroidism in premenopausal women and associated morbidity2008Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, nr 1, s. 47-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Primary hyperparathyroidism (PHPT) and associated morbidity are comprehensively assessed in elderly females; however, less is known of the disease in younger women. OBJECTIVES: Our objectives were to estimate the prevalence of mild disturbances in calcium homeostasis, which could be analogous with early PHPT, in a premenopausal population, and determine the potential presence of associated morbidity. DESIGN: Initial results from this longitudinal study are from 2002-2004. SETTING: We conducted a population-based screening of serum (s)-calcium in conjunction with routine mammography. PARTICIPANTS: Participants included premenopausal women, 40-50 yr of age (n = 1900). Cases fulfilling previously evaluated biochemical criteria for PHPT (n=214) were matched to controls (n = 214). MAIN OUTCOME MEASUREMENTS: All participants underwent investigation, including screening of parameters of calcium homeostasis, dual x-ray absorptiometry, and body mass index assessment, and filled out extensive health and quality of life (SF-36) questionnaires. Participants were divided into four groups depending on the relation between s-calcium/intact PTH. Statistical comparisons between cases and controls as well as among the four groups were performed to evaluate morbidity. RESULTS: The prevalence of assumed mild PHPT, i.e. inappropriate intact PTH value in relation to total s-calcium, was estimated to be 5.1% (n = 96). Women with mild disturbances in calcium homeostasis had statistically significant lower bone mineral density in the proximal femur and femoral neck, higher body mass index, and lower scores for vitality and general health in the analysis of SF-36. CONCLUSIONS: Mild disturbances in calcium homeostasis in premenopausal women were more prevalent than previously thought and were associated with obesity, lower bone mineral density, and decreased quality of life.

  • 260.
    Siproudhis, L.
    et al.
    CHU Pontchaillou, Rennes, France..
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Emmanuel, A.
    Univ Coll Hosp, 235 Euston Rd, London, England..
    Walker, D.
    Norgine Ltd, Norgine House,Widewater Pl,Moorhall Rd, Uxbridge UB9 6NS, Middx, England..
    Shing, R. Ng Kwet
    Norgine Ltd, Norgine House,Widewater Pl,Moorhall Rd, Uxbridge UB9 6NS, Middx, England..
    Pediconi, C.
    Norgine Ltd, Norgine House,Widewater Pl,Moorhall Rd, Uxbridge UB9 6NS, Middx, England..
    Pilot, J.
    Norgine Ltd, Norgine House,Widewater Pl,Moorhall Rd, Uxbridge UB9 6NS, Middx, England..
    Wexner, S.
    Cleveland Clin Florida, Weston, FL USA..
    Scholefield, J.
    Univ Nottingham Hosp, Div Surg, Nottingham NG7 2UH, England..
    Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response2016Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 31, nr 6, s. 1205-1216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Faecal incontinence (FI) is distressing, significantly reduces quality of life (QoL) and has few pharmacological treatments. The alpha(1)-adrenoceptor agonist NRL001 (1R,2S-methoxamine hydrochloride) improves anal sphincter tone. NRL001 efficacy was evaluated by changes in Wexner scores at week 4 vs. baseline in NRL001-treated patients compared with placebo. Impact of NRL001 on QoL and safety were also assessed. Four hundred sixty-six patients received NRL001 (5, 7.5 or 10 mg) or placebo as suppository, once daily over 8 weeks. Wexner score, Vaizey score and QoL were analysed at baseline, week 4 and week 8. FI episodes and adverse events were recorded in diaries. At week 4, mean reductions in Wexner scores were -3.0, -2.6, -2.6 and -2.4 for NRL001 5, 7.5, 10 mg and placebo, respectively. All reduced further by week 8. As placebo responses also improved, there was no significant treatment effect at week 4 (p = 0.6867) or week 8 (p = 0.5005). FI episode frequency improved for all patients, but not significantly compared with placebo (week 4: p = 0.2619, week 8: p = 0.5278). All patients' QoL improved, but not significantly for all parameters (p > 0.05) except depression/self-perception at week 4 (p = 0.0102) and week 8 (p = 0.0069), compared with placebo. Most adverse events were mild and judged probably or possibly related to NRL001. All groups demonstrated improvement in efficacy and QoL compared with baseline. NRL001 was well-tolerated without serious safety concerns. Despite the improvement in all groups, there was no statistically significant treatment effect, underlining the importance of relating results to a placebo arm.

  • 261.
    Sjöberg, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Larsson, Märit
    Nielsen, Anne-Lie
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Acute severe ulcerative colitis in a population based cohort (ICURE): Outcome and complications of medical and surgical treatmentArtikkel i tidsskrift (Fagfellevurdert)
  • 262. Skoglund, Johanna
    et al.
    Song, Bo
    Dalén, Johan
    Dedorson, Stefan
    Edler, David
    Hjern, Fredrik
    Holm, Jörn
    Lenander, Claes
    Lindforss, Ulrik
    Lundqvist, Nils
    Olivecrona, Hans
    Olsson, Louise
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Rutegård, Jörgen
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Törnqvist, Anders
    Houlston, Richard S.
    Lindblom, Annika
    Lack of an association between the TGFBR1*6A variant and colorectal cancer risk2007Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 13, nr 12, s. 3748-3752Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies.

    Experimental Design: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted.

    Results: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A.

    Conclusion: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.

  • 263.
    Sköldberg, Filip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Olen, Ola
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden.
    Ekbom, Anders
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Schmidt, Peter T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Digest Dis, Stockholm, Sweden.
    Appendectomy and Risk of Subsequent Diverticular Disease Requiring Hospitalization: A Population-Based Case-Control Study2018Inngår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 61, nr 7, s. 830-839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case-control studies. OBJECTIVE: The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease. DESIGN: This was a population-based case-control study. SETTINGS: The study was based on national healthcare and population registers. PATIENTS: We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects. MAIN OUTCOME MEASURES: The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use. RESULTS: A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24-1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23-1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61-3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71-5.83)), but the association was still present 20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12-1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10-1.28)). LIMITATIONS: Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors. CONCLUSIONS: The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. See Video Abstract at http://links.lww.com/DCR/A604.

  • 264.
    Sköldberg, Filip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Svensson, Tobias
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Olen, Ola
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden..
    Hjern, Fredrik
    Danderyd Hosp, Div Surg, Dept Clin Sci, Stockholm, Sweden..
    Schmidt, Peter T.
    Karolinska Inst, Dept Med, Unit Gastroenterol & Hepatol, Stockholm, Sweden..
    Ljung, Rickard
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden..
    A population-based case-control study on statin exposure and risk of acute diverticular disease2016Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, nr 2, s. 203-210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. Material and methods: A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed <= 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. Results: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). Conclusions: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.

  • 265.
    Smedh, Kenneth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Sverrisson, Ingvar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hartmann's procedure vs abdominoperineal resection with intersphincteric dissection in patients with rectal cancer: a randomized multicentre trial (HAPIrect)2016Inngår i: BMC Surgery, ISSN 1471-2482, E-ISSN 1471-2482, Vol. 16, artikkel-id 43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The use of Hartmann's procedure in the old and frail and/or in patients with fecal incontinence is increasing, even though some data have reported high postoperative rates of pelvic abscesses. Abdominoperineal excision with intersphincteric dissection has been proposed as a better alternative and is performed increasingly both nationally and internationally. However, no studies have been performed to support this. The aim of this study is to randomize patients between Hartmann's procedure and abdominoperineal excision with intersphincteric dissection and compare post-operative surgical morbidity and quality of life. The hypothesis is that intersphincteric abdominoperineal excision provides less pelvic and perineal morbidity. Methods/design: In this multicentre randomized controlled study, Hartmann's procedure will be compared with intersphincteric abdominoperineal excision in patients with rectal cancer unsuitable for an anterior resection. The patients are operated in different ways around the ano-rectum, otherwise the same procedure is performed with total mesorectal excision and all will receive a colostomy. The one-month postoperative control will focus on post-operative surgical complications, especially the perineal-pelvic, reoperations and other interventions. After one year, late complications such as pain in the perineal or pelvic area or disorders such as secretion or bleeding from the anorectal stump will be recorded and a follow-up of quality of life performed. Histological and oncological data will also be recorded, the latter up to 5 years post-operatively. Discussion: The HAPIrect trial is the first randomized controlled trial comparing standard low Hartmann's procedure with intersphincteric abdominoperineal excision in patients with rectal cancer with the aim of categorizing the post-operative surgical morbidity.

  • 266. Strigård, K
    et al.
    Folkesson, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Gunnarsson, U
    The Easy-X magnetic stoma connector system: A future concept for stomal dressing?2013Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 28, nr 3, s. 371-374Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM:

    A considerable proportion of stoma patients are disabled for various reasons and are elderly. To be able to dress their stoma themselves is of crucial importance for their integrity and social life. This study evaluates a novel stomal dressing system based on a magnetic connector-the Easy-X system.

    METHOD:

    Twenty patients (8 women, mean age of 40-89 years) with a well-functioning colostomy tested the Easy-X system for 6 weeks. The system was judged by the patients using a multiple choice scale, and by the stoma nurses using a 10-grade VAS.

    RESULTS:

    Eighteen of 20 patients completed the trial. Ten patients rated the Easy-X as better than their ordinary system, 3 as equal to and 4 deemed it inferior. Despite this, only three were prepared to change to the Easy-X system. Eleven of 18 patients experienced discomfort with the new adhesive plate. Three patients suffered leakage less often and five patients more often than with their ordinary system. Stoma nurse ratings were available for 14 patients. Their evaluation of the magnetic connector in the Easy-X system was positive in eight cases, neutral in one case and negative in three cases. Global impression ratings were 3 positive, 3 negative and 5 neutral.

    CONCLUSION:

    The Easy-X system showed potential advantages over conventional stomal dressing systems, but the system must be improved in terms of a varied assortment of dressing products enabling individual fitting before a larger trial can be carried out on disabled patients. Furthermore, the increased use of metal has to be handled with an ecologic recycling system.

    WHAT IS NEW IN THIS PAPER:

    A new stomal dressing system with a magnetic connector has potential advantages over conventional stomal dressings for disabled persons.

  • 267. Strigård, K
    et al.
    Gurmu, A
    Näsvall, P
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Gunnarsson, U
    Intrastomal 3D ultrasound: an inter- and intra-observer evaluation2013Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 28, nr 1, s. 43-47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The aim of this study was to determine intra- and interobserver reliability in 3D intrastomal ultrasound imaging of parastomal hernia and protrusion. METHOD: A total of 40 patients were investigated. Two or three physicians evaluated the images twice, 1 month apart. RESULTS: Inter-observer agreement was 72 % with a kappa value 0.59. For the last 10 patients there was an agreement of 80 % with a kappa value of 0.70. Intraobserver agreement was 80 % for one observer and 95 % for the other. The learning curve levelled out at around 30 patients. CONCLUSION: Considering the learning curve of 30 patients, 3D intrastomal ultrasound is a reliable investigation method. 3D intrastomal ultrasonography has the potential to be the investigation of choice to differentiate between a bulge, a hernia, or a protrusion.

  • 268.
    Sundström, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Edlund, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Lindell, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Birgisson, Helgi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    KRAS analysis in colorectal carcinoma: analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice2010Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 10, s. 660-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised.Methods: The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples.Results: Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13 mutations.Conclusions: KRAS mutation detection using Pyrosequencing was evaluated on a consecutive set of clinical CRC samples. Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the mutation status in routine formalin-fixed CRC samples, even in tissues with a low tumor cell content.

  • 269.
    Sundín, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Carlsson, L
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Carlsson, J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat: Aspects of tumour implantation site and mode of antibody administration1993Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 32, nr 7-8, s. 877-885Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.

  • 270.
    Sundín, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Computed tomography of experimental liver metastases using an iodinated hepatocyte-specific lipid emulsion: a correlative study in the nude rat1994Inngår i: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 29, nr 11, s. 963-969Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    RATIONALE AND OBJECTIVES:

    A hepatocyte-specific iodinated lipid emulsion, NRI 757, was used for detection of experimental hepatic metastases.

    MATERIALS AND METHODS:

    The study was performed in a correlative model of multiple hepatic metastases from a human colonic cancer implanted in the nude rat.

    RESULTS:

    After intravenous injection, normal liver parenchyma remained enhanced for several hours, whereas the uptake in hepatic metastases was negligible. A liver-to-lesion contrast of 45 Hounsfield units (HU) was obtained at a dose of 1 mL NRI 757/kg body weight (BW). In a lesion-by-lesion analysis of 177 metastases ranging in size from 1 to 32 mm, the mean +/- standard deviation overall detection rate for native scanning and contrast-enhanced scanning in vivo and post mortem, 20 +/- 0.4%, 53 +/- 5.2%, and 55 +/- 4.0%, respectively and 28%, 84%, and 82%, retrospectively. When metastatic size also was considered, for native scanning the maximum detection rate of 61% was reached for 8- to 10-mm lesions, whereas for contrast-enhanced computed tomography scanning, 100% of the 5- to 7-mm lesions and 42% of the 1- to 2-mm nodules were detected.

    CONCLUSION:

    The use of NRI 757 improved the diagnostic yield considerably.

  • 271.
    Sundín, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat1992Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 18, nr 6, s. 615-623Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.

  • 272. Suo, Tao
    et al.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Qin, Xin-Yu
    Hyperthermic intraperitoneal chemotherapy for gastric and colorectal cancer in Mainland China2011Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 17, nr 8, s. 1071-1075Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To investigate the current status of peritoneal carcinomatosis (PC) management, as well as the usage of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in mainland China. METHODS: A potentially curative therapeutic strategy for selecting patients with PC, known as "Techniques", consists of CRS in combination with HIPEC. A systemic search of published works and clinical trials was performed. Additional papers were retrieved by crosschecking references and obtaining information from Chinese oncologists and relevant conferences. One hundred and one papers and one registered clinical trial on HIPEC were included. RESULTS: A literature review identified 86 hospitals in 25 out of all 31 areas of mainland China that perform HIPEC. The earliest report included in our survey was published in 1993. Different approaches to HIPEC have been utilized, i.e. palliative, prophylactic, and possibly curative treatment. Only one center has consistently performed HIPEC according to the "Sugarbaker Protocol", which involves evaluating the extent of PC with peritoneal cancer index and the results of CRS with the completeness of cytoreduction. Positive preliminary results were reported: 7 of 21 patients with PC survived, free of tumors, during an 8-43-mo follow-up period. Hyperthermic strategies that include HIPEC have been practiced for a long time in mainland China, whereas the "Sugarbaker Protocol/Techniques" has been only rarely implemented in China. The Peritoneal Surface Oncology Group International hosts a biannual workshop with the intent to train more specialists in this field and provide support for the construction of quality treatment centers, especially in developing countries like China, whose population is huge and has a dramatically increased incidence of cancer. CONCLUSION: To popularize Sugarbaker Protocol/Techniques in mainland China in PC management arising from gastric cancer or colorectal cancer will be the responsibility of the upcoming Chinese Peritoneal Surface Oncology Group.

  • 273.
    Sverrisson, Ingvar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Folkvaljon, Folke
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Anastomotic leakage after anterior resection in patients with rectal cancer previously irradiated for prostate cancerManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Introduction: There are little data on the post-operative outcome of anterior resection (AR) for rectal cancer in men who had received radiotherapy for prostate cancer previously. The aim of this study was to assess the rate of anastomotic leakage (AL) after AR in these patients.

    Methods: All men who underwent bowel resection because of rectal cancer between 2000 and 2016 and had been diagnosed previously with prostate cancer were identified by linking the Swedish Colorectal Cancer Registry with the National Prostate Cancer Register. The medical records of men who underwent AR and had previously received radiotherapy for prostate cancer were reviewed.

    Results: In total, 13299 men had undergone a bowel resection for rectal cancer, 188 of whom had previously received radiotherapy for prostate cancer. Among those who had received radiation therapy, 59 men (31%) had an AR: 50 men (85%) received a diverting ileostomy, 42 men (71%) had an American Society of Anesthesiologists score of 1–2 and 36 men (61%) had tumour stage 1–2. AL was found in 12/59 men (20%), one of whom had a re-laparotomy. There was no 90-day mortality.

    Conclusions: In the combined national population-based registries, a minority of patients with rectal cancer had an AR after previous radiotherapy for prostate cancer. These patients were healthy with early cancer stages and, in this selected group of patients, the AL rate was much lower than that reported previously.

  • 274.
    Sverrisson, Ingvar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Folkvaljon, Folke
    Uppsala universitet.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Anastomotic leakage after anterior resection in patients with rectal cancer previously irradiated for prostate cancer2019Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 45, nr 3, s. 341-346Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction:

    There are little data on the post-operative outcome of anterior resection (AR) for rectal cancer in men who had received radiotherapy for prostate cancer previously. The aim of this study was to assess the rate of anastomotic leakage (AL) after AR in these patients.

    Methods:

    All men who underwent bowel resection because of rectal cancer between 2000 and 2016 and had been diagnosed previously with prostate cancer were identified by linking the Swedish Colorectal Cancer Registry with the National Prostate Cancer Register. The medical records of men who underwent AR and had previously received radiotherapy for prostate cancer were reviewed.

    Results:

    In total, 13299 men had undergone a bowel resection for rectal cancer, 188 of whom had previously received radiotherapy for prostate cancer. Among those who had received radiation therapy, 59 men (31%) had an AR: 50 men (85%) received a diverting ileostomy, 42 men (71%) had an American Society of Anesthesiologists score of 1-2 and 36 men (61%) had tumour stage 1-2. AL was found in 12/59 men (20%), one of whom had a re-laparotomy. There was no 90-day mortality.

    Conclusions:

    In the combined national population-based registries, a minority of patients with rectal cancer had an AR after previous radiotherapy for prostate cancer. These patients were healthy with early cancer stages and, in this selected group of patients, the AL rate was much lower than that reported previously.

  • 275.
    Sverrisson, Ingvar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hosseinali Khani, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Low risk of intra-abdominal infections in rectal cancer patients treated with Hartmann's procedure: a report from a national registry2018Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 33, nr 3, s. 327-332Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To describe the postoperative surgical complications in patients with rectal cancer undergoing Hartmann's procedure (HP). Data were retrieved from the Swedish Colorectal Cancer Registry for all patients with rectal cancer undergoing HP in 2007-2014. A retrospective analysis was performed using prospectively recorded data. Characteristics of patients and risk factors for intra-abdominal infection and re-laparotomy were analysed. Of 10,940 patients resected for rectal cancer, 1452 (13%) underwent HP (median age, 77 years). The American Society of Anesthesiologists (ASA) score was 3-4 in 43% of patients; 15% had distant metastases and 62% underwent a low HP. The intra-abdominal infection rate was 8% and re-laparotomy rate was 10%. Multivariable logistic regression analysis identified preoperative radiotherapy (OR, 1.78; 95% CI, 1.14-2.77), intra-operative bowel perforation (OR, 1.99; 95% CI, 1.08-3.67), T4 tumours (OR, 1.68; 95% CI 1.04-2.69) and female gender (OR, 1.73; 95% CI, 1.15-2.61) as risk factors for intra-abdominal infection. ASA score 3-4 (OR, 1.62; 95% CI, 1.12-2.34), elevated BMI (OR, 1.05; 95% CI, 1.02-1.09) and female gender (OR, 2.06; CI, 1.41-3.00) were risk factors for re-laparotomy after HP. The rate of intra-abdominal infection was not increased after a low HP. Despite older age and co-morbidities including more advanced cancer, patients undergoing Hartmann's procedure had low rates of serious postoperative complications and re-laparotomy. A low HP was not associated with a higher rate of intra-abdominal infection. HP seems to be appropriate for old and frail patients with rectal cancer.

  • 276.
    Sverrisson, Ingvar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Smedh, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hartmann's procedure in rectal cancer: a population-based study of postoperative complications2015Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, nr 2, s. 181-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hartmann's procedure for rectal cancer patients is increasingly performed but few studies have reported the postoperative outcome. The purpose was to report postoperative complications and analyse risk factors in rectal cancer patients operated with Hartmann's procedure. To describe the selection and postoperative complication patterns, all bowel-resected rectal cancer patients were included. Population-based data were from the county of Vastmanland, Sweden. All rectal cancer patients operated with an elective bowel resection between 1996 and 2012 were included. Demographics and postoperative complications were prospectively registered and data retrospectively analysed. Of the 624 patients included, 396 (64 %) were operated with an anterior resection, 159 (25 %) with an abdominoperineal excision and 69 (11 %) a Hartmann's procedure of which 90 % were low Hartmann's. Patients operated with a Hartmann's procedure were significantly older, had higher ASA-score, poorer WHO performance score and lower serum albumin levels. Operative time for Hartmann's procedure was a median of 49 and 99 min shorter than after anterior resection and abdominoperineal excision, respectively, and entailed less bleeding. Complications related to the pelvic and perineal dissections were more common after abdominoperineal excision compared with anterior resection and Hartmann's procedure (32 vs. 9 and 13 %, p < 0.001). Few rectal cancer patients, operated with Hartmann's procedure, developed pelvic complications despite a higher age, more co-morbidities, metastases in different localities and functional inferiority when compared with the patients operated with anterior resection or abdominoperineal excision. Hartmann's procedure is a valid alternative procedure in the old and frail rectal cancer patient.

  • 277.
    Söderbäck, Harald
    et al.
    Department of Surgery, Capio St Göran, Stockholm, Sweden.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Hellman, Per
    Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Sandblom, Gabriel
    Karolinska Institutet, CLINTEC, Stockholm, Sweden.
    Prophylactic Resorbable Synthetic Mesh to Prevent Wound Dehiscence and Incisional Hernia in High High-risk Laparotomy: A Pilot Study of Using TIGR Matrix Mesh2016Inngår i: Frontiers in surgery, ISSN 2296-875X, Vol. 3, artikkel-id 28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Wound dehiscence and incisional hernia are potentially serious complications following abdominal surgery, especially if performed through a midline incision. Although prophylactic reinforcement with on-lay mesh has been shown to reduce this risk, a permanent mesh carries the risk of seroma formation, infection, and persistent pain. The aim of this study was to assess the safety of a reabsorbable on-lay mesh to reinforce the midline suture in patients with high risk for wound dehiscence or incisional hernia.

    METHOD:

    Sixteen patients with three or more risk factors for wound dehiscence or incisional hernia were included. A TIGR(®) Matrix mesh, composed of a mixture of 40% copolymer fibers of polyglycolide, polylactide, and polytrimethylene carbonate and 60% copolymer fibers of polylactide and polytrimethylene carbonate, was placed on the aponeurosis with an overlap of five on either side and fixated with continuous monofilament polydioxanone suture. All postoperative complications were registered at clinical follow-up.

    RESULTS:

    Mean follow-up was 9 months. One patient developed a seroma that needed drainage and antibiotic treatment. One patient had a wound infection that needed antibiotic treatment. There was no complication requiring a reoperation. No wound dehiscence or incisional hernia was seen.

    CONCLUSION:

    On-lay placement of TIGR(®) Matrix is safe and may provide a feasible way of reinforcing the suture line in patients with high risk for postoperative wound dehiscence or incisional hernia. Larger samples are required, however, if one is to draw any conclusion regarding the safety and effectiveness of this technique.

  • 278.
    Thorisson, Arnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Department of Radiology, Västmanlands Hospital, Västerås, Sweden..
    Nikberg, Maziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Torkzad, Michael R
    Department of Diagnostic Radiology, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
    Laurell, Helena
    Colorectal Unit, Department of Surgery, Landstinget Dalarna, Mora, Sweden..
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Diagnostic Accuracy of Acute Diverticulitis with Non-Enhanced Low-Dose CT2018Inngår i: Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Purpose: To evaluate the diagnostic accuracy of non-enhanced low-dose computed tomography (LDCT) in acute colonic diverticulitis with contrast-enhanced standard-dose CT (SDCT) as the reference method.

    Materials and Methods: Consecutive patients with clinically suspected diverticulitis were included from two hospitals between January and October 2017. All patients underwent LDCT followed by SDCT. All CT examinations were assessed for signs of diverticulitis, complications, and other diagnoses by three independent radiologists (two radiology consultants and one fourth-year resident) using SDCT as the reference method. Sensitivity, specificity, and agreement were calculated.

    Results: In total, 149 patients (median age 68, 107 women) were included; 107 had diverticulitis on standard CT. Sensitivity for diverticulitis using LDCT was 100%; the values were 99% for consulting radiologists and 92% for the radiology resident. Specificity was 100% for both consultants and 84% for the resident. Sensitivity for identification of complications was 74%, 60%, and 54%, respectively. Twenty-six patients had other causes of abdominal symptoms on standard CT, 23 (88%) of whom were diagnosed correctly on LDCT. One case of splenic infarction and two cases of segment colitis were missed on LDCT.

    Conclusion: The diagnostic accuracy of LDCT was high for acute diverticulitis. Therefore, it is recommended as a standard method that should help to reduce radiation dose and cost. LDCT had lower sensitivity for complications, although discrimination between an inflamed diverticulum and small pericolic abscess accounted for a proportion of the discrepancies.

  • 279.
    Thorisson, Arnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Torkzad, M R
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Chabok, Abbas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    CT imaging for prediction of complications and recurrence in acute uncomplicated diverticulitis2016Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 31, nr 2, s. 451-457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The first randomized clinical trial of antibiotics in uncomplicated diverticulitis (the AVOD study) showed no benefit of antibiotics. The aim of this study was to re-evaluate the computed tomography (CT) scans of the patients in the AVOD study to find out whether there were CT findings that were missed and to study whether CT signs in uncomplicated diverticulitis could predict complications or recurrence.

    METHODS: The CT scan images from patients included in the AVOD study were re-evaluated and graded by two independent reviewers for different signs of diverticulitis, including complications, such as extraluminal gas or the presence of an abscess.

    RESULTS: Of the 623 patients included in the study, 602 CT scans were obtained and re-evaluated. Forty-four (7 %) patients were found to have complications on the admitting CT scan that had been overlooked. Twenty-seven had extraluminal gas and 17 had an abscess. Four of these patients deteriorated and required surgery, but the remaining patients improved without complications. Of the 18 patients in the no-antibiotic group, in whom signs of complications on CT were overlooked, 15 recovered without antibiotics. No CT findings in patients with uncomplicated diverticulitis could predict complications or recurrence.

    CONCLUSION: No CT findings that could predict complications or recurrence were found. A weakness in the initial assessment of the CT scans to detect extraluminal gas and abscess was found but, despite this, the majority of patients recovered without antibiotics. This further supports the non-antibiotic strategy in uncomplicated diverticulitis.

  • 280. Tiefenthal, Marit
    et al.
    Nilsson, Per J.
    Johansson, Robert
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    The Effects of Short-Course Preoperative Irradiation on Local Recurrence Rate and Survival in Rectal Cancer: A Population-Based Nationwide Study2011Inngår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 54, nr 6, s. 672-680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Preoperative irradiation with 5 x 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer. OBJECTIVE: The aim of this study was to determine whether the same favorable effects could be observed in a population-based study. DESIGN: This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry. SETTINGS: This study examined population-based data from Sweden. PATIENTS: All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry. INTERVENTIONS: Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann's procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm). MAIN OUTCOME MEASURES: Five-year cumulative local recurrence and survival rates. RESULTS: The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors. CONCLUSIONS: In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).

  • 281.
    Tiselius, C
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Gunnarsson, U
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Patients with rectal cancer receiving adjuvant chemotherapy have an increased survival: a population-based longitudinal study2013Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, nr 1, s. 160-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The aim of this study was to investigate whether or not the use of adjuvant chemotherapy in stage III rectal cancer varies between regions and over time, and if this has had an effect on survival rates.

    Patients and methods

    Patients from the Uppsala/Örebro region below 75 years-of-age, operated 1995-2002 and registered in the Swedish Rectal Cancer Register, were monitored between 1995 and September 2008. A multivariate Cox proportional hazard regression model was used for analysis. Overall survival was described using the Kaplan-Meier method.

    Results

    Four hundred and thirty-six patients with stage III rectal cancer were included. Adjuvant chemotherapy was given to 42% of the patients (proportions varying from 13% to 77% among counties), and there were substantial increases over time. The 5-year overall survival was 65.8% [95% confidence interval (CI) 50-84] for patients having adjuvant chemotherapy compared with 45.6% (95% CI 39-52) for patients not treated with chemotherapy. The multivariate hazard ratio for death was 0.65 (95% CI 0.5-0.8) for patients treated with adjuvant chemotherapy.

    Conclusions

    The use of adjuvant chemotherapy for rectal cancer has increased, but varies considerably between hospitals/counties. In this cohort, those having adjuvant chemotherapy had a longer overall survival.

  • 282.
    Torkzad, Michael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Casta, Nicoleta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Comparison between MRI and CT in prediction of peritoneal carcinomatosis index (PCI) in patients undergoing cytoreductive surgery in relation to the experience of the radiologist2015Inngår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 111, nr 6, s. 746-751Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    To compare CT and MRI for peritoneal carcinomatosis index (PCI) assessment and to compare assessments made by the radiologist based on their experiences.

    METHOD AND MATERIALS:

    MRI and CT of abdomen and pelvis were performed on 39 prospectively followed by surgery directly. Two blinded radiologists with different experience levels evaluated PCI separately on different occasions on 19 cases initially and later on the remaining 20. The agreement between the radiologists' assessment and surgical findings in total and per site were recorded.

    RESULTS:

    Total PCI: The experienced radiologist was able to assess total tumor burden correctly on both CT and MRI (kappa = 1.0). For the inexperienced radiologist the assessment was better on CT (kappa = 0.73) compared to MRI (kappa = 0.58). Different sites: The experienced radiologist showed high agreement with kappa = 0.77 for MRI and 0.80 for CT. Corresponding figures were 0.39 and 0.60 for the inexperienced radiologist. For the second phase the agreement levels increased for the inexperienced radiologist increased to 0.80 and 0.70, respectively.

    CONCLUSION:

    CT and MRI are equal when read by experienced radiologist. CT shows better results when read by an inexperienced radiologist compared to MRI, however the results of the latter can easily be improved.

  • 283.
    Torkzad, Michael R
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Comparison of different magnetic resonance imaging sequences for assessment of fistula-in-ano2014Inngår i: World Journal of Radiology, ISSN 1949-8470, E-ISSN 1949-8470, Vol. 6, nr 5, s. 203-209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM:

    To assess agreement between different forms of T2 weighted imaging (T2WI), and post-contrast T1WI in the depiction of fistula tracts, inflammation, and internal openings with that of a reference test.

    METHODS:

    Thirty-nine consecutive prospective cases were enrolled. The following sequences were used for T2WI: 2D turbo-spin-echo (2D T2 TSE); 3D T2 TSE; short tau inversion recovery (STIR); 2D T2 TSE with fat saturation performed in all patients. T1WI were either a 3D T1-weighted prepared gradient echo sequence with fat saturation or a 2D T1 fat saturation [Spectral presaturation with inversion (SPIR)]. Agreement for each sequence for determination of fistula extension, internal openings, and the presence of active inflammation was assessed separately and blindly against a reference test comprised of follow-up, surgery, endoscopic ultrasound, and assessment by an independent experienced radiologist with access to all images.

    RESULTS:

    Fifty-six fistula tracts were found: 2 inter-sphincteric, 13 trans-sphincteric, and 24 with additional tracts. The best T2 weighted sequence for depiction of fistula tracts was 2D T2 TSE (Cohen's kappa = 1.0), followed by 3D T2 TSE (0.88), T2 with fat saturation (0.54), and STIR (0.19). Internal openings were best seen on 2D T2 TSE (Cohen's kappa = 0.88), followed by 3D T2 TSE (0.70), T2 with fat saturation (0.54), and STIR (0.31). Detection of inflammation showed Cohen's kappa of 0.88 with 2D T2 TSE, 0.62 with 3D T2 TSE, 0.63 with STIR, and 0.54 with T2 with fat saturation. STIR, 3D T2 TSE, and T2 with fat saturation did not make any contributions compared to 2D T2 TSE. Post-contrast 3D T1 weighted prepared gradient echo sequence with fat saturation showed better agreement in the depiction of fistulae (Cohen's kappa = 0.94), finding internal openings (Cohen's kappa = 0.97), and evaluating inflammation (Cohen's kappa = 0.94) compared to post-contrast 2D T1 fat saturation or SPIR where the corresponding figures were 0.71, 0.66, and 0.87, respectively. Comparing the best T1 and T2 sequences showed that, for best results, both sequences were necessary.

    CONCLUSION:

    3D T1 weighted sequences were best for the depiction of internal openings and active inflammatory components, while 2D T2 TSE provided the best assessment of fistula extension.

  • 284.
    Torkzad, Michael R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Karlsson, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    MRI for assessment of anal fistula2010Inngår i: Insights into imaging, ISSN 1869-4101, Vol. 1, nr 2, s. 62-71Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Magnetic resonance imaging (MRI) is the best imaging modality for preoperative assessment of patients with anal fistula. MRI helps to accurately demonstrate disease extension and predict prognosis. This in turn helps make therapy decisions and monitor therapy. The pertinent anatomy, fistula classification and MRI findings will be discussed.

  • 285.
    Torkzad, Michael R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review2010Inngår i: Insight into Imaging, ISSN 1869-4101, E-ISSN 1869-4101, Vol. 1, nr 4, s. 245-267Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience.

  • 286. Trudel, Judith
    et al.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Adjuvant therapy for colorectal cancer2007Inngår i: The ASCRS Textbook of Colon and Rectal Surgery / [ed] Bruce G. Wolff, James W. Fleshman, David E. Beck, John H. Pemberton, Steven D. Wexner, James M. Church, Patricia L. Roberts, Julio Garcia-Aguilar, Theodore J. Saclarides & Michael J. Stamos, New York: Springer , 2007, s. 437-445Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 287.
    Tugues, Sònia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Roche, Francis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Noguer, Oriol
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Bhoi, Sujata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Padhan, Narendra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Åkerud, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Honjo, Satoshi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Selvaraju, Ram Kumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Mazzone, Massimiliano
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Claesson-Welsh, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Histidine-Rich Glycoprotein Uptake and Turnover Is Mediated by Mononuclear Phagocytes.2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 9, s. e107483-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Histidine-rich glycoprotein (HRG) is implicated in tumor growth and metastasis by regulation of angiogenesis and inflammation. HRG is produced by hepatocytes and carried to tissues via the circulation. We hypothesized that HRG's tissue distribution and turnover may be mediated by inflammatory cells. Biodistribution parameters were analyzed by injection of radiolabeled, bioactive HRG in the circulation of healthy and tumor-bearing mice. 125I-HRG was cleared rapidly from the blood and taken up in tissues of healthy and tumor-bearing mice, followed by degradation, to an increased extent in the tumor-bearing mice. Steady state levels of HRG in the circulation were unaffected by the tumor disease both in murine tumor models and in colorectal cancer (CRC) patients. Importantly, stromal pools of HRG, detected in human CRC microarrays, were associated with inflammatory cells. In agreement, microautoradiography identified 125I-HRG in blood vessels and on CD45-positive leukocytes in mouse tissues. Moreover, radiolabeled HRG bound in a specific, heparan sulfate-independent manner, to differentiated human monocytic U937 cells in vitro. Suppression of monocyte differentiation by systemic treatment of mice with anti-colony stimulating factor-1 neutralizing antibodies led to reduced blood clearance of radiolabeled HRG and to accumulation of endogenous HRG in the blood. Combined, our data show that mononuclear phagocytes have specific binding sites for HRG and that these cells are essential for uptake of HRG from blood and distribution of HRG in tissues. Thereby, we confirm and extend our previous report that inflammatory cells mediate the effect of HRG on tumor growth and metastatic spread.

  • 288. Valentini, Vincenzo
    et al.
    Aristei, Cynthia
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Minsky, Bruce D
    Beets-Tan, Regina
    Borras, Jose M
    Haustermans, Karin
    Maingon, Philippe
    Overgaard, Jens
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Quirke, Phil
    Schmoll, Hans-Joachim
    Sebag-Montefiore, David
    Taylor, Irving
    Van Cutsem, Eric
    Van de Velde, Cornelius
    Cellini, Numa
    Latini, Paolo
    Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2)2009Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 92, nr 2, s. 148-163Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO). METHODS: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", and "minimum consensus". RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe.

  • 289. Valentini, Vincenzo
    et al.
    Beets-Tan, Regina
    Borras, Josep M.
    Krivokapić, Zoran
    Leer, Jan Willem
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Rödel, Claus
    Schmoll, Hans Joachim
    Scott, Nigel
    Van de Velde, Cornelius
    Verfaillie, Christine
    Evidence and research in rectal cancer2008Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 87, nr 3, s. 449-474Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The main evidences of epidemiology, diagnostic imaging, pathology, surgery, radiotherapy, chemotherapy and follow-up are reviewed to optimize the routine treatment of rectal cancer according to a multidisciplinary approach. This paper reports on the knowledge shared between different specialists involved in the design and management of the multidisciplinary ESTRO Teaching Course on Rectal Cancer. The scenario of ongoing research is also addressed. In this time of changing treatments, it clearly appears that a common standard for large heterogeneous patient groups have to be substituted by more individualised therapies based on clinical-pathological features and very soon on molecular and genetic markers. Only trained multidisciplinary teams can face this new challenge and tailor the treatments according to the best scientific evidence for each patient.

  • 290. van de Velde, C. J. H.
    et al.
    Boelens, P. G.
    Tanis, P. J.
    Espin, E.
    Mroczkowski, P.
    Naredi, P.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Ortiz, H.
    Rutten, H. J.
    Breugom, A. J.
    Smith, J. J.
    Wibe, A.
    Wiggers, T.
    Valentini, V.
    Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: Science, opinions and experiences from the experts of surgery2014Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, nr 4, s. 454-468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

  • 291. van de Velde, Cornelis J. H.
    et al.
    Aristei, Cynthia
    Boelens, Petra G.
    Beets-Tan, Regina G. H.
    Blomqvist, Lennart
    Borras, Josep M.
    van den Broek, Colette B. M.
    Brown, Gina
    Coebergh, Jan-Willem
    Van Cutsem, Eric
    Espin, Eloy
    Gore-Booth, Jola
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Haustermans, Karin
    Henning, Geoffrey
    Iversen, Lene H.
    van Krieken, J. Han
    Marijnen, Corrie A. M.
    Mroczkowski, Pawel
    Nagtegaal, Iris
    Naredi, Peter
    Ortiz, Hector
    Pahlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Quirke, Philip
    Roedel, Claus
    Roth, Arnaud
    Rutten, Harm J. T.
    Schmoll, Hans J.
    Smith, Jason
    Tanis, Pieter J.
    Taylor, Claire
    Wibe, Arne
    Gambacorta, Maria Antonietta
    Meldolesi, Elisa
    Wiggers, Theo
    Cervantes, Andres
    Valentini, Vincenzo
    EURECCA colorectal: Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 13, s. 2784-2790Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.

    Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method.

    Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members.

    Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

  • 292. van de Velde, Cornelis J. H.
    et al.
    Boelens, Petra G.
    Borras, Josep M.
    Coebergh, Jan-Willem
    Cervantes, Andres
    Blomqvist, Lennart
    Beets-Tan, Regina G. H.
    van den Broek, Colette B. M.
    Brown, Gina
    Van Cutsem, Eric
    Espin, Eloy
    Haustermans, Karin
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Iversen, Lene H.
    van Krieken, J. Han
    Marijnen, Corrie A. M.
    Henning, Geoffrey
    Gore-Booth, Jola
    Meldolesi, Elisa
    Mroczkowski, Pawel
    Nagtegaal, Iris
    Naredi, Peter
    Ortiz, Hector
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Quirke, Philip
    Roedel, Claus
    Roth, Arnaud
    Rutten, Harm
    Schmoll, Hans J.
    Smith, Jason J.
    Tanis, Pieter J.
    Taylor, Claire
    Wibe, Arne
    Wiggers, Theo
    Gambacorta, Maria A.
    Aristei, Cynthia
    Valentini, Vincenzo
    EURECCA colorectal: Multidisciplinary management: European consensus conference colon & rectum2014Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, nr 1, s. UNSP 1.e1-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Care for patients with colon and rectal cancer has improved in the last 20 years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.

    Methods

    The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process.

    Results

    The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members.

    Conclusions

    Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

  • 293. Van den Broek, C. B. M.
    et al.
    van Gijn, W.
    Bastiaannet, E.
    Moller, B.
    Johansson, R.
    Elferink, M. A. G.
    Wibe, A.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Iversen, L. H.
    Penninckx, F.
    Valentini, V.
    van de Velde, C. J. H.
    Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands2014Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, nr 12, s. 1789-1796Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in pen-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up.

  • 294.
    Van der Speeten, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    A Pharmacokinetic and Pharmacodynamic Rationale for Perioperative Cancer Chemotherapy in Patients with Peritoneal Carcinomatosis2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Peritoneal carcinomatosis (PC) is a common manifestation of both gastrointestinal and gynecologic malignancies. Until recently, this condition was considered beyond curative intent treatment. Since the 1980s, new treatment strategies combining cytoreductive surgery (CRS) with perioperative intraperitoneal and intravenous chemotherapy have emerged. The underlying hypothesis considers CRS responsible for the removal of the macroscopic disease and that perioperative chemotherapy should address the residual microscopic disease. These new treatment regimens have presented encouraging clinical results that contrast with prior failure. The parameters for perioperative chemotherapy are mainly extrapolated from literature on peritoneal dialysis and data from systemic chemotherapy. The overall aim of this thesis was to provide a pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal (IP) and intravenous (IV) chemotherapy in PC patients and, to assess its toxicity. After intraoperative IV administration of 5-fluorouracil or ifosfamide, substantial levels of these drugs were found inside the peritoneal fluid and tumor nodules (Papers I and II). This created a pharmacologically advantageous situation whereby a normothermic administered IV drug was subject to the effect of the local hyperthermia in the peritoneal fluid and tumor nodule. High levels of 5-fluouracil, ifosfamide and doxorubicin were observed inside the tumor nodules (Papers I, II and III) and, the identical pharmacokinetic advantage (expressed as Area Under the Curve (AUC) IP/IV ratios)) resulted in different drug levels of doxorubicin according to the density of the tumor nodules (Paper III). These data stressed the importance of pharmacodynamic variables such as tumor nodule density, size, and, vascularity. Therefore, the tumor nodule is proposed as a more appropriate pharmacological endpoint than AUC ratios. After IP Mitomycin C administration in PC patients with a contracted abdomen, mitomycin clearance from the abdomen decreased (Paper IV), which indicated  these patients at risk of under-treatment. Consequently, these pharmacologic data indicate a change in dosimetry for these treatment protocols might be warranted according to the diffusion area. Although diffusional vectors are viewed the main driving force for these treatment protocols, only pharmacokinetic variables such as dose, volume and duration are considered. As pharmacodynamic variables are equally important in the pharmacological assessment of cytotoxic effect, the tumor nodule was proposed as the center of a new conceptual model (Paper I). Mitomycin C data on non-metabolizers ( Paper IV) indicated the cytotoxicity of these cancer chemotherapy protocols is at the level of the individual tumor nodules. The morbidity and mortality of a new bidirectional intraoperative chemotherapy regimen in PC patients was analyzed (Paper V) which provided a means for identifying subsets of patients at risk for increased toxicity. This thesis provides pharmacokinetic and pharmacodynamic guidance for improving perioperative chemotherapy treatment strategies in PC patients and reports its toxicity.

    Delarbeid
    1. Pharmacology of perioperative 5-fluorouracil
    Åpne denne publikasjonen i ny fane eller vindu >>Pharmacology of perioperative 5-fluorouracil
    2010 (engelsk)Inngår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 102, nr 7, s. 730-735Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    The purpose of this study was to analyze our current pharmacologic data regarding the perioperative use of 5-fluorouracil in the treatment of peritoneal surface malignancies.

    Methods

    Twenty-nine patients with peritoneal carcinomatosis from appendiceal malignancy were included in this pharmacological study.

    Results

    In the nine patients who received early postoperative intraperitoneal chemotherapy, the area under the curve for intraperitoneal 5-fluorouracil was 43,000 (+20,300) µg/ml x minutes and for intravenous 5-fluorouracil was 157 (+99) µg/ml x minutes.  The area under the curve ratio was 422 (+360). In 20 patients who received intravenous 5-fluorouracil in the operating room intraperitoneal 5-fluorouracil levels maintained a higher level as compared to the intravenous drug level over the 90 minutes of drug sampling. The area under the curve ratio of peritoneal fluid to plasma was 2.3 (+1.3). The area under curve ratio of peritoneal fluid to tumor nodules was 9.9 (+9.8).  The area under the curve ratio of plasma to tumor nodules was 5.2 (+4.7).

    Conclusions

    By modulating the route or timing of administration of 5-fluorouracil, it becomes a pharmacologic advantageous molecule in patients with peritoneal carcinomatosis of an appendiceal malignancy. 5-fluorouracil remains the cornerstone of the perioperative management of peritoneal carcinomatosis of gastrointestinal origin.

    Emneord
    5-fluorouracil, intraperitoneal chemotherapy, intravenous chemotherapy, pharmacokinetics, pharmacodynamics, appendiceal cancer
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-133273 (URN)10.1002/jso.21702 (DOI)000285281300006 ()21104923 (PubMedID)
    Tilgjengelig fra: 2010-11-04 Laget: 2010-11-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    2. Pharmacokinetic Study of Perioperative Intravenous Ifosfamide
    Åpne denne publikasjonen i ny fane eller vindu >>Pharmacokinetic Study of Perioperative Intravenous Ifosfamide
    2011 (engelsk)Inngår i: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, s. 185092-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    The use of cancer chemotherapy as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Various combinations of intraperitoneal and systemic chemotherapy used with moderate hyperthermia constitute the cytotoxic component of this therapy.  Ifosfamide, being a heat synergized drug, may be an important chemotherapy agent to use when attempting to optimize this treatment strategy. 

    Materials and methods

    16 Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5 - 42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy.  Using high pressure liquid chromatography (HPLC) the concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm.

    Results

    Urine ifosfamide and 4-hydroxyifosfamide concentrations exceeded those within the plasma and peritoneal fluid throughout the 90 minutes of drug infusion.  Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion; however, at 60 minutes after infusion ceased, the peritoneal fluid and plasma concentrations were equivalent.  Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations.

    Conclusions

    Clear understanding of the pharmacology of perioperative intraperitoneal hyperthermia combined with systemic chemotherapy may provide important information for the design of treatment regimens.  4-hydroxyifosfamide within cancerous tissue suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room. 

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-133274 (URN)10.1155/2011/185092 (DOI)
    Tilgjengelig fra: 2010-11-04 Laget: 2010-11-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin
    Åpne denne publikasjonen i ny fane eller vindu >>A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin
    2009 (engelsk)Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 63, nr 5, s. 799-805Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    PURPOSE: A pharmacologic analysis of intracavitary doxorubicin in the treatment of patients with intracavitary cancer dissemination was performed to further evaluate the possible benefits of this treatment modality. METHODS: Twenty appendiceal malignancy patients with peritoneal carcinomatosis (PC), three appendiceal malignancy patients with direct extension into the pleural cavity, 20 patients with peritoneal mesothelioma and one patient with pleural mesothelioma were available for pharmacologic monitoring. After intraperitoneal or intrapleural administration of doxorubicin, plasma and peritoneal fluid samples were obtained at 15, 30, 45, 60 and 90 min in all patients. After intrapleural administration, plasma and pleural fluid samples were collected at similar intervals. Tumor and normal tissues were obtained when available. Doxorubicin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: Intraperitoneal doxorubicin showed a prolonged retention in the peritoneal cavity. Doxorubicin concentrations in tumor tissue were consistently elevated above intraperitoneal concentrations from 30 through 90 min. For appendiceal malignancy, the concentrations of doxorubicin were significantly higher in minimally aggressive mucinous tumors. Pleural chemotherapy solutions retained doxorubicin to a greater extent than peritoneal fluid. CONCLUSIONS: Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.

    Emneord
    Intraperitoneal chemotherapy, Intrapleural chemotherapy, Doxorubicin, Pharmacokinetics, Pharmacodynamics, Appendiceal cancer, Peritoneal mesothelioma, Pleural mesothelioma
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-103497 (URN)10.1007/s00280-008-0800-0 (DOI)000263787600006 ()18654746 (PubMedID)
    Tilgjengelig fra: 2009-05-19 Laget: 2009-05-19 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Changes Induced by Surgical and Clinical Factors in the Pharmacology of Intraperitoneal Mitomycin C in 145 Patients with Peritoneal Carcinomatosis
    Åpne denne publikasjonen i ny fane eller vindu >>Changes Induced by Surgical and Clinical Factors in the Pharmacology of Intraperitoneal Mitomycin C in 145 Patients with Peritoneal Carcinomatosis
    Vise andre…
    2011 (engelsk)Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 68, nr 1, s. 147-156Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated.

    MATERIALS AND METHODS: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined.

    RESULTS: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma.

    CONCLUSIONS: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-133275 (URN)10.1007/s00280-010-1460-4 (DOI)000292048100016 ()20857115 (PubMedID)
    Tilgjengelig fra: 2010-11-04 Laget: 2010-11-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    5. Toxicity of a Uniform Combined Bidirectional Hyperthermic and Perioperative Intraperitoneal Chemotherapy Regimen after Cytoreductive Surgery in 147 Peritoneal Surface Malignancy Patients
    Åpne denne publikasjonen i ny fane eller vindu >>Toxicity of a Uniform Combined Bidirectional Hyperthermic and Perioperative Intraperitoneal Chemotherapy Regimen after Cytoreductive Surgery in 147 Peritoneal Surface Malignancy Patients
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background

    Currently, the treatment of peritoneal surface malignancy is managed in selected patients by the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The chemotherapy agents utilized are selected from response rates in the treatment of gross disease and from pharmacologic studies. These agents are then subjected to morbidity/mortality studies to establish the safety of the treatment. The aim of this study was to analyze the morbidity and mortality of a new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after cytoreductive surgery.

    Materials and Methods

    Patients (n=147) with peritoneal surface malignancy received a uniform treatment of cytoreductive surgery combined with intraoperative chemotherapy. HIPEC with mitomycin C and doxorubicin was supplemented with intravenous 5-fluorouracil and leucovorin. In 65 patients, additional early postoperative intraperitoneal (EPIC) 5-fluorouracil was added to the HIPEC for the first four postoperative days. The clinical factors were cataloged prospectively and any adverse events (AE) were tabulated. 

    Results

    In 85% of patients, complete cytoreduction was achieved. There was an increase in grade IV AE in patients with incomplete cytoreduction (p<0.04) and in patients receiving fresh frozen plasma (p<0.001). For both grades III and IV AE, a right colon resection increased morbidity (p<0.02) and chemotherapy treatment HIPEC plus EPIC increased morbidity, compared to HIPEC alone (p<0.05). The overall morbidity (grades I-IV) was 64% and mortality was 0.6%.

    Conclusion

    The new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after CRS can be safely applied in peritoneal carcinomatosis patients.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-133276 (URN)
    Tilgjengelig fra: 2010-11-04 Laget: 2010-11-04 Sist oppdatert: 2018-01-12bibliografisk kontrollert
  • 295.
    Van der Speeten, Kurt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Alderman, R
    Washington Cancer Institute, Washington DC, USA.
    Edwards, G
    Washington Cancer Institute, Washington DC, USA.
    Marquardt, C
    Washington Cancer Institute, Washington DC, USA.
    Stuart, O.A.
    Washington Cancer Institute, Washington DC, USA.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sugarbaker, P.H.
    Washington Cancer Institute, Washington DC, USA.
    Toxicity of a Uniform Combined Bidirectional Hyperthermic and Perioperative Intraperitoneal Chemotherapy Regimen after Cytoreductive Surgery in 147 Peritoneal Surface Malignancy PatientsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background

    Currently, the treatment of peritoneal surface malignancy is managed in selected patients by the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The chemotherapy agents utilized are selected from response rates in the treatment of gross disease and from pharmacologic studies. These agents are then subjected to morbidity/mortality studies to establish the safety of the treatment. The aim of this study was to analyze the morbidity and mortality of a new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after cytoreductive surgery.

    Materials and Methods

    Patients (n=147) with peritoneal surface malignancy received a uniform treatment of cytoreductive surgery combined with intraoperative chemotherapy. HIPEC with mitomycin C and doxorubicin was supplemented with intravenous 5-fluorouracil and leucovorin. In 65 patients, additional early postoperative intraperitoneal (EPIC) 5-fluorouracil was added to the HIPEC for the first four postoperative days. The clinical factors were cataloged prospectively and any adverse events (AE) were tabulated. 

    Results

    In 85% of patients, complete cytoreduction was achieved. There was an increase in grade IV AE in patients with incomplete cytoreduction (p<0.04) and in patients receiving fresh frozen plasma (p<0.001). For both grades III and IV AE, a right colon resection increased morbidity (p<0.02) and chemotherapy treatment HIPEC plus EPIC increased morbidity, compared to HIPEC alone (p<0.05). The overall morbidity (grades I-IV) was 64% and mortality was 0.6%.

    Conclusion

    The new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after CRS can be safely applied in peritoneal carcinomatosis patients.

  • 296.
    Van der Speeten, Kurt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Stuart, O. A.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sugarbaker, P. H.
    A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin2009Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 63, nr 5, s. 799-805Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: A pharmacologic analysis of intracavitary doxorubicin in the treatment of patients with intracavitary cancer dissemination was performed to further evaluate the possible benefits of this treatment modality. METHODS: Twenty appendiceal malignancy patients with peritoneal carcinomatosis (PC), three appendiceal malignancy patients with direct extension into the pleural cavity, 20 patients with peritoneal mesothelioma and one patient with pleural mesothelioma were available for pharmacologic monitoring. After intraperitoneal or intrapleural administration of doxorubicin, plasma and peritoneal fluid samples were obtained at 15, 30, 45, 60 and 90 min in all patients. After intrapleural administration, plasma and pleural fluid samples were collected at similar intervals. Tumor and normal tissues were obtained when available. Doxorubicin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: Intraperitoneal doxorubicin showed a prolonged retention in the peritoneal cavity. Doxorubicin concentrations in tumor tissue were consistently elevated above intraperitoneal concentrations from 30 through 90 min. For appendiceal malignancy, the concentrations of doxorubicin were significantly higher in minimally aggressive mucinous tumors. Pleural chemotherapy solutions retained doxorubicin to a greater extent than peritoneal fluid. CONCLUSIONS: Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.

  • 297.
    Van der Speeten, Kurt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Stuart, O. Anthony
    Washington Cancer Institute, Washington D.C., USA.
    Chang, David
    Westat, Rockville, MD, USA.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sugarbaker, Paul H.
    Washington Cancer Institute, Washington D.C., USA.
    Changes Induced by Surgical and Clinical Factors in the Pharmacology of Intraperitoneal Mitomycin C in 145 Patients with Peritoneal Carcinomatosis2011Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 68, nr 1, s. 147-156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated.

    MATERIALS AND METHODS: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined.

    RESULTS: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma.

    CONCLUSIONS: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.

  • 298.
    Van der Speeten, Kurt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Stuart, O.A.
    Washington Cancer Institute, Washington D.C., USA.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sugarbaker, Paul H.
    Washington Cancer Institute, Washington D.C., USA.
    Pharmacokinetic Study of Perioperative Intravenous Ifosfamide2011Inngår i: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, s. 185092-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The use of cancer chemotherapy as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Various combinations of intraperitoneal and systemic chemotherapy used with moderate hyperthermia constitute the cytotoxic component of this therapy.  Ifosfamide, being a heat synergized drug, may be an important chemotherapy agent to use when attempting to optimize this treatment strategy. 

    Materials and methods

    16 Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5 - 42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy.  Using high pressure liquid chromatography (HPLC) the concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm.

    Results

    Urine ifosfamide and 4-hydroxyifosfamide concentrations exceeded those within the plasma and peritoneal fluid throughout the 90 minutes of drug infusion.  Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion; however, at 60 minutes after infusion ceased, the peritoneal fluid and plasma concentrations were equivalent.  Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations.

    Conclusions

    Clear understanding of the pharmacology of perioperative intraperitoneal hyperthermia combined with systemic chemotherapy may provide important information for the design of treatment regimens.  4-hydroxyifosfamide within cancerous tissue suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room. 

  • 299.
    Van der Speeten, Kurt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Stuart, O.A.
    Washington Cancer Institute, Washington D.C., USA.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Sugarbaker, P.H.
    Washington Cancer Institute, Washington D.C., USA.
    Pharmacology of perioperative 5-fluorouracil2010Inngår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 102, nr 7, s. 730-735Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The purpose of this study was to analyze our current pharmacologic data regarding the perioperative use of 5-fluorouracil in the treatment of peritoneal surface malignancies.

    Methods

    Twenty-nine patients with peritoneal carcinomatosis from appendiceal malignancy were included in this pharmacological study.

    Results

    In the nine patients who received early postoperative intraperitoneal chemotherapy, the area under the curve for intraperitoneal 5-fluorouracil was 43,000 (+20,300) µg/ml x minutes and for intravenous 5-fluorouracil was 157 (+99) µg/ml x minutes.  The area under the curve ratio was 422 (+360). In 20 patients who received intravenous 5-fluorouracil in the operating room intraperitoneal 5-fluorouracil levels maintained a higher level as compared to the intravenous drug level over the 90 minutes of drug sampling. The area under the curve ratio of peritoneal fluid to plasma was 2.3 (+1.3). The area under curve ratio of peritoneal fluid to tumor nodules was 9.9 (+9.8).  The area under the curve ratio of plasma to tumor nodules was 5.2 (+4.7).

    Conclusions

    By modulating the route or timing of administration of 5-fluorouracil, it becomes a pharmacologic advantageous molecule in patients with peritoneal carcinomatosis of an appendiceal malignancy. 5-fluorouracil remains the cornerstone of the perioperative management of peritoneal carcinomatosis of gastrointestinal origin.

  • 300. van Gijn, W.
    et al.
    van de Velde, C. J. H.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Improving quality of cancer care through surgical audit2010Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 36, nr Suppl 1, s. S23-26Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Quality of healthcare is a hot topic and this is especially true for cancer care. New surgical techniques and effective neoadjuvant treatment regimens have significantly improved colorectal cancer outcome. Nevertheless, there seem to be substantial differences in quality of care between European countries, hospitals and doctors. To reduce hospital variation, most initiatives aim on selective referral, encouraging patients to seek care in high-volume hospitals, where cancer care is concentrated to site-specialist multidisciplinary teams. As an alternative to volume-based referral, hospitals and surgeons can also improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. European national audit registries in surgical oncology have led to improvements with a greater impact on survival than any of the adjuvant therapies currently under study. Moreover, they offer the possibility to perform research on patient groups that are usually excluded from clinical trials. Nevertheless, between European countries remain differences in outcome and treatment schedules that cannot be easily explained. The European CanCer Organisation (ECCO) has recognised these importances and created the 'European Registration of Cancer Care' (EURECCA) framework to develop a European colorectal audit structure. EURECCA will advance future treatment improvements and spread these to all European cancer patients. It provides opportunities to treat elderly and comorbid patients evidence based while it offers an unique insight in social-economical healthcare matters such as the consequences of commercialisation, treatment availability and screening initiatives. As such, ECCO has established the basis for a strong, multidisciplinary audit structure with the commitment to improve cancer care for every European cancer patient.

34567 251 - 300 of 318
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