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  • 151.
    Karlbom, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Surgery for the failed ileorectal or caecorectal anastomosis in chronic constipation2013In: Reconstructive Surgery of the Rectum, Anus and Perineum / [ed] Andrew P. Zbar, Robert D. Madoff, Steven Wexner, London: Springer, 2013, p. 267-271Chapter in book (Refereed)
    Abstract [en]

    This chapter discusses the reasons for clinical failure after subtotal or total colectomy when the indication is principally for chronic constipation. Well-known side effects of this treatment include diarrhea and urgency as well as fecal incontinence in up to 30 % of operated cases. As an alternative to a more radical resection, segmental left colectomy has been proposed, although the reported results have not been particularly successful: recent comparative, non-randomized data have shown a higher incidence of persistent constipation with a continued requirement for laxatives and enemas postoperatively in those patients undergoing a cecorectal anastomosis when compared with those undergoing an ileorectal anastomosis. The incidence of troublesome diarrhea and fecal incontinence does not, however, seem to differ between these operative groups. This chapter outlines the treatment options available and the approach used when ileorectal or cecorectal anastomoses performed for patients with intractable constipation do not function appropriately.

  • 152.
    Kindler, Csaba
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Chabok, Abbas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Shetye, Jayant
    Department of Pathology, Vastmanland's Hospital Vasteras, Vasteras, Sweden.
    Dafnis, George
    Malar Hosp, Dept Surg, Eskilstuna, Sweden..
    Nikberg, Maziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Detection of Free Cancer Cells in Pelvic Lavage with Double Immunocytochemistry at Rectal Cancer Surgery2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1563-1568Article in journal (Refereed)
    Abstract [en]

    Background/Aim: The aim of the present study was to describe a double immunocytochemical staining method for detecting free cancer cells after rectal cancer surgery and to evaluate their extent and prognostic role. Materials and Methods: Immunocytochemistry was performed using antibodies against cytokeratin 20/caudal-typehomeobox transcription factor 2 (CDX2) and mucin glycoprotein-2 (MUC2)/p53 protein. The study included 29 patients with infraperitoneal rectal cancer who underwent bowel resection and four controls. The pelvic lavage was retrieved at the start of laparotomy, after total mesorectal excision and after abdominal lavage with sterile water. Results: Free cancer cells were detected with the double immunocytochemical method in the two controls with carcinomatosis and one control with sigmoidal cancer. None of the patients with rectal tumours had presence of free cancer cells. Conclusion: Immunocytochemical analysis of peritoneal lavage was feasible and negative in patients with infraperitoneal rectal cancer. Further studies are encouraged to investigate the clinical relevance in cases with free cancer cells after incomplete total mesorectal excision.

  • 153. Kodeda, K.
    et al.
    Johansson, R.
    Zar, N.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dahlberg, M.
    Skullman, S.
    Lindmark, G.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Martling, A.
    Time trends, improvements and national auditing of rectal cancer management over an 18-year period2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 9, p. O168-O179Article in journal (Refereed)
    Abstract [en]

    Aim: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series.

    Method: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded.

    Results: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited.

    Conclusion: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

  • 154. Kodeda, K.
    et al.
    Nathanaelsson, L.
    Jung, B.
    Olsson, H.
    Jestin, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sjovall, A.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Syk, I.
    Population-based data from the Swedish Colon Cancer Registry2013In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 100, no 8, p. 1100-1107Article in journal (Refereed)
    Abstract [en]

    Background Evaluating the external validity of clinical trials requires knowledge not only of the study population but also of a relevant reference population. The main aim of this study was to present data from a large, contemporary, population-based cohort of patients with colonic cancer. Methods Data on patients diagnosed between 2007 and 2011 were extracted from the Swedish Colon Cancer Registry. The data, registered prospectively in a national population of almost 10 million, included over 99 per cent of all diagnosed adenocarcinomas of the colon. Results This analysis included 18889 patients with 19526 tumours (3 center dot 0 per cent had synchronous tumours). The sex distribution was fairly equal, and the median age was 74 center dot 1 (interquartile range 65-81) years. The overall and relative (cancer-specific) survival rates after 3 years were 62 center dot 7 and 71 center dot 4 per cent respectively. Some 88 center dot 0 per cent of the patients were operated on, and 83 center dot 8 per cent had tumours resected. Median blood loss during bowel resection was 200 (mean 311) ml, and the median operating time was 160min; 5 center dot 6 per cent of the procedures were laparoscopic. Preoperative chemotherapy was administered to 2 center dot 1 per cent of patients; postoperative chemotherapy was planned in 90 center dot 1 per cent of fit patients aged less than 75 years with stage III disease. In patients operated on in an emergency setting (21 center dot 5 per cent), the preoperative evaluation was less extensive, the proportion of R0 resections was lower, and the outcomes were poorer, in both the short and long term. Conclusion These population-based data represent good-quality reference points.

  • 155.
    Krause, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ultrasonography findings and tumour quantification in patients with pseudomyxoma peritonei2012In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 81, no 4, p. 648-651Article in journal (Refereed)
    Abstract [en]

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

  • 156. Kressner, Marit
    et al.
    Bohe, Måns
    Cedermark, Björn
    Dahlberg, Michael
    Damber, Lena
    Lindmark, Gudrun
    Ojerskog, Björn
    Sjödahl, Rune
    Johansson, Robert
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The impact of hospital volume on surgical outcome in patients with rectal cancer2009In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 9, p. 1542-1549Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study was designed to investigate, in a population-based setting, the surgical outcome in patients with rectal cancer according to the hospital volume. METHODS: Since 1995 all patients with rectal cancer have been registered in the Swedish Rectal Cancer Registry. Hospitals were classified, according to number treated per year, as low-volume, intermediate-volume, or high-volume hospitals (<11, 11-25, or >25 procedures per year). Postoperative mortality, reoperation rate within 30 days, local recurrence rate, and overall five-year survival were studied. For postoperative morbidity and mortality the whole cohort from 1995 to 2003 (n = 10,425) was used. For cancer-related outcome only, those with five-year follow-ups, from 1995 to 1998, were used (n = 4,355). RESULTS: In this registry setting the postoperative mortality rate was 3.6% in low-volume hospitals, and 2.2% in intermediate-volume and high-volume hospitals (P = 0.002). The reoperation rate was 10%, with no differences according to volume. The overall local recurrence rates were 9.4%, 9.3%, and 7.5%, respectively (P = 0.06). Significant difference was found among the nonirradiated patients (P = 0.004), but not among the irradiated patients (P = 0.45). No differences were found according to volume in the absolute five-year survival. CONCLUSION: Postoperative mortality and local recurrence in nonirradiated patients were lower in high-volume hospitals. No difference was seen between volumes in reoperation rates, overall local recurrence, or absolute five-year survival.

  • 157. Larsson, Anna
    et al.
    Fridberg, Marie
    Gaber, Alexander
    Nodin, Björn
    Leveen, Per
    Jönsson, Göran
    Uhlen, Mathias
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 282-Article in journal (Refereed)
    Abstract [en]

    Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.

  • 158.
    Larsson, Anna H.
    et al.
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Lehn, Sophie
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Wangefjord, Sakarias
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Karnevi, Emelie
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Kuteeva, Eugenia
    AlbaNova Univ Ctr, Atlas Antibodies AB, Stockholm, Sweden..
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nodin, Björn
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Eberhard, Jakob
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer2016In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 14, article id 128Article in journal (Refereed)
    Abstract [en]

    Background: Podocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane protein that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). The aim of this study was to examine the associations between PODXL and EGFR expression in CRC in vitro and in vivo.

    Methods: EGFR expression was analysed in tumours from three independent patient cohorts; cohort 1 (n = 533), cohort 2 (n = 259) and cohort 3 (n = 310), previously analysed for immunohistochemical PODXL expression and KRAS and BRAF mutations (cohort 1 and 3). Levels of EGFR and PODXL were determined by western blot in six different CRC cell lines.

    Results: High expression of PODXL was significantly associated with high EGFR expression (p < 0.001) in all three cohorts, and with BRAF mutation (p < 0.001) in cohort 1 and 3. High EGFR expression correlated with BRAF mutation (p < 0.001) in cohort 1. High EGFR expression was associated with adverse clinicopathological factors and independently predicted a reduced 5-year overall survival (OS) in cohort 1 (HR 1.77; 95 % CI 1.27-2.46), cohort 2 (HR 1.58; 95 % CI 1.05-2.38) and cohort 3 (HR 1.83; 95 % CI 1.19-2.81). The highest risk of death within 5 years was observed in patients with tumours displaying high expression of both EGFR and PODXL in cohort 1 and 3 (HR 1.97; 95 % CI 1.18-3.28 and HR 3.56; 95 % CI 1.75-7.22, respectively). Western blot analysis showed a uniform expression of PODXL and EGFR in all six examined CRC cell lines.

    Conclusions: The results from this study demonstrate that high expression of EGFR is an independent factor of poor prognosis in CRC. Moreover, strong links have been uncovered between expression of the recently proposed biomarker candidate PODXL with EGFR expression in CRC in vivo and in vitro, and with BRAF mutation in vivo. High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival. These findings suggest a potential functional link in CRC between PODXL, EGFR and BRAF, all originating from chromosome 7, which may be highly relevant in the clinical setting and therefore merit future in-depth study.

  • 159.
    Laurell, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hansson, Lars-Erik
    Gunnarsson, Ulf
    Is there an association between adult coeliac disease and non-specific abdominal pain?: Reply2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 7, p. 898-898Article in journal (Refereed)
  • 160.
    Laurell, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hansson, L-E
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Acute diverticulitis: clinical presentation and differential diagnostics2007In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 9, no 6, p. 496-501Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the clinical presentation of acute diverticulitis in an emergency department and to characterize the natural history of diverticulitis in the short perspective. Comparisons are made with an important differential diagnosis, nonspecific abdominal pain (NSAP). METHOD: Patients admitted to our hospital with abdominal pain of up to 7 days' duration were registered prospectively using a detailed schedule for history, symptoms and signs, from 1 February 1997 to 1 June 2000. Of 3349 patients initially included, 3073 (92%) were eligible for follow up after 1-3 years. RESULTS: Acute diverticulitis was the final diagnosis in 145 patients and NSAP in 1142 patients. The incidence of hospitalized patients with diverticulitis was 47 per year and 100 000 population, with a mean hospital stay of 3.3 days. Patients with diverticulitis, more frequently than NSAP, had a longer history and laboratory signs of inflammatory activity. Isolated left abdominal tenderness was more common in diverticulitis, whereas isolated right abdominal tenderness was more common in NSAP. Duration of symptoms on arrival was independent of age and was not correlated to C-reactive protein, leucocytes or body temperature. Sensitivity of diverticulitis as primary diagnosis was 64% and specificity 97%. Corresponding figures for NSAP were 43% and 90% respectively. Age and gender did not influence diagnostic accuracy or risk of surgery. CONCLUSION: Diverticulitis differs significantly from NSAP in clinical presentation and laboratory parameters. Sensitivity of primary diagnosis for diverticulitis and NSAP was low.

  • 161. Lehmann, J-P
    et al.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Efficacy of LIFT for recurrent anal fistula2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 5, p. 592-595Article in journal (Refereed)
    Abstract [en]

    AIM:

    Ligation of the intersphincteric fistula tract (LIFT) is a novel sphincter-preserving technique for anal fistula. This pilot study was designed to evaluate the results in patients with a recurrent fistula.

    METHOD:

    Seventeen patients [nine men; median age 49 (range, 30-76) years] with a recurrent trans-sphincteric fistula were treated with a LIFT procedure between June 2008 and February 2011. All were followed prospectively for a median of 16 (range, 5-27) weeks with clinical examination. Fifteen followed for 13.5 (range, 8-26) months by clinical examination also had three-dimensional (3D) anal ultrasound.

    RESULTS:

    The duration of the procedure was 35 (range, 18-70) min. One patient developed a small local haematoma and one had a subcutaneous infection, but otherwise there was no morbidity. At follow up, 11 (65%) patients had a successful closure, two (12%) had a remaining sinus and four (23%) had a persistent fistula. The incidence of persistent or recurrent fistulae at 13.5 months was six (40%) of 15 patients. No de novo faecal incontinence was reported.

    CONCLUSION:

    LIFT is a safe procedure for patients with recurrent anal fistula, with healing at short-term and medium-term follow-up comparable with or superior to that of other sphincter-preserving techniques. Larger studies with a longer follow up are needed to define the ultimate role of LIFT in patients with recurrence.

  • 162.
    Lindell, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Biochemistry.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lang, Matti A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Variable Expression of CYP and Pgp Genes in the Human Small Intestine2003In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 33, no 6, p. 493-499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome p450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes.

    METHODS:

    The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed.

    RESULTS:

    Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively.

    CONCLUSIONS:

    Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation.

  • 163.
    Linder, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Letter to the editor: stercoral perforation of the sigmoid colon possibly associated with anticholinergic drugs or opiates2016In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 1, no 7, p. 1383-1384Article in journal (Refereed)
  • 164. Lindstedt, Sandra
    et al.
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hlebowicz, Joanna
    Comparative study of the microvascular blood flow in the intestinal wall during conventional negative pressure wound therapy and negative pressure wound therapy using paraffin gauze over the intestines in laparostomy2012In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 9, no 2, p. 150-155Article in journal (Refereed)
    Abstract [en]

    Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) than with other kinds of wound management. We have recently shown that NPWT decreases the blood flow in the intestinal wall, and that the blood flow could be restored by inserting a protective disc over the intestines. The aim of the present study was to investigate whether layers of Jelonet (TM) (Smith & Nephew) dressing (paraffin tulle gras dressing made from open weave gauze) over the intestines could protect the intestines from hypoperfusion. Midline incisions were made in ten pigs and were subjected to treatment with NPWT with and without four layers of Jelonet over the intestines. The microvascular blood flow was measured in the intestinal wall before and after the application of topical negative pressures of -50, -70 and -120 mmHg, using laser Doppler velocimetry. Baseline blood flow was defined as 100% in all settings. The blood flow was significantly reduced, to 61 +/- 7% (P < 0.001), after the application of -50 mmHg using conventional NPWT, and to 62 +/- 7% (P < 0.001) after the application of -50 mmHg with Jelonet dressings between the dressing and the intestines. The blood flow was significantly reduced, to 38 +/- 5% (P < 0.001), after the application of -70 mmHg, and to 42 +/- 6% (P < 0.001) after the application of -70 mmHg with Jelonet dressings. The blood flow was significantly reduced, to 34 +/- 9% (P < 0.001), after the application of -120 mmHg, and to 38 +/- 6% (P < 0.001) after the application of -120 mmHg with Jelonet dressings. The use of four layers of Jelonet over the intestines during NPWT did not prevent a decrease in microvascular blood flow in the intestinal wall.

  • 165. Lindstedt, Sandra
    et al.
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hlebowicz, Joanna
    The effect of negative wound pressure therapy on haemodynamics in a laparostomy wound model2013In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 10, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    We have recently shown that negative pressure wound therapy (NPWT) induces a decrease in microvascular blood flow in the small intestinal loop close to the dressing. The effect of NPWT is thus thought to be local. In this study, we investigate whether the application of NPWT in laparostomy affects the haemodynamics. Midline incisions were made in six pigs followed by NPWT at 120 mmHg for 20 minutes. The cardiac output, mean systemic arterial pressure, mean pulmonary artery pressu re, central venous pressure, left atrial pressure and superior mesenteric artery blood flow were recorded. The blood flow in a small branch of the superior mesenteric artery was then recorded under NPWT between 50 and 175 mmHg. Cardiac output was not affected by NPWT [P = not significant (n.s.)]. Neither the mean arterial pressure nor the mean pulmonary artery pressure was affected by NPWT (P = n.s.). Negative pressures of 50, 75, 100 and 125 mmHg did not alter the blood flow in the small branch of the superior mesenteric artery (P = n.s.). After application of 150 mmHg, a significant decrease in blood flow was seen (P < 0 center dot 01), while the application of 175 mmHg resulted in only a slight decrease in blood flow (P = n.s.). The effect of NPWT in laparotomy seems to be local and to have no influence on central haemodynamics or the blood flow to the superior mesenteric artery.

  • 166. Lindstedt, Sandra
    et al.
    Malmsjö, Malin
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hlebowicz, Joanna
    Ingemansson, Richard
    Microvascular Blood Flow Changes in the Small Intestinal Wall During Conventional Negative Pressure Wound Therapy and Negative Pressure Wound Therapy Using a Protective Disc Over the Intestines in Laparostomy2011In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 255, no 1, p. 171-175Article in journal (Refereed)
    Abstract [en]

    Objectives: Blood flow changes in the intestines during conventional negative pressure wound therapy (NPWT), and NPWT using a protective disc over the intestines in laparostomy.

    Background: Higher closure rates of the open abdomen have been reported with NPWT compared with other kinds of wound management. However, the method has been associated with increased development of fistulae. We have compared the changes in blood flow in the intestinal wall using conventional NPWT and NWPT with a protective disc between the intestines and the vacuum source.

    Methods: Midline incisions were made in 10 pigs and either conventional NPWT or NPWT with a disc over the intestines was applied. The microvascular blood flow was measured in the intestinal wall before and after the application of topical negative pressures of -50, -70, and -120 mmHg, using laser Doppler velocimetry.

    Results: The blood flow was significantly decreased (by 24%) after the application of conventional NPWT at -50 mmHg, compared with a slight decrease (2%) after the application of NWPT with a protective disc (P < 0.05). The blood flow was significantly decreased (by 54%) after the application of conventional NPWT at -120 mmHg, compared with a slight decrease (17%) after application of NPWT using a protective disc (P < 0.001).

    Conclusions: Inserting a disc between the intestines and the vacuum source in NPWT protects the intestines from ischemia. The decreased blood flow in the intestinal wall may induce ischemia, which could promote the development of intestinal fistulae.

  • 167. Lindstedt, Sandra
    et al.
    Malmsjö, Malin
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hlebowicz, Joanna
    Ingemansson, Richard
    Pressure transduction and fluid evacuation during conventional negative pressure wound therapy of the open abdomen and NPWT using a protective disc over the intestines2012In: BMC Surgery, ISSN 1471-2482, E-ISSN 1471-2482, Vol. 12, p. 4-Article in journal (Refereed)
    Abstract [en]

    Background: Negative pressure wound therapy (NPWT) has gained acceptance among surgeons, for the treatment of open abdomen, since very high closure rates have been reported with this method, compared to other kinds of wound management for the open abdomen. However, the method has occasionally been associated with increased development of fistulae. We have previously shown that NPWT induces ischemia in the underlying small intestines close to the vacuum source, and that a protective disc placed between the intestines and the vacuum source prevents the induction of ischemia. In this study we compare pressure transduction and fluid evacuation of the open abdomen with conventional NPWT and NPWT with a protective disc.

    Methods: Six pigs underwent midline incision and the application of conventional NPWT and NPWT with a protective disc between the intestines and the vacuum source. The pressure transduction was measured centrally beneath the dressing, and at the anterior abdominal wall, before and after the application of topical negative pressures of -50, -70 and -120 mmHg. The drainage of fluid from the abdomen was measured, with and without the protective disc.

    Results: Abdominal drainage was significantly better (p < 0. 001) using NPWT with the protective disc at -120 mmHg (439 +/- 25 ml vs. 239 +/- 31 ml), at -70 mmHg (341 +/- 27 ml vs. 166 +/- 9 ml) and at -50 mmHg (350 +/- 50 ml vs. 151 +/- 21 ml) than with conventional NPWT. The pressure transduction was more even at all pressure levels using NPWT with the protective disc than with conventional NPWT.

    Conclusions: The drainage of the open abdomen was significantly more effective when using NWPT with the protective disc than with conventional NWPT. This is believed to be due to the more even and effective pressure transduction in the open abdomen using a protective disc in combination with NPWT.

  • 168.
    Liu, Yang
    et al.
    NPO Support Peritoneal Surface Malignancy Treatme, Kyoto, Japan;Kishiwada Tokushukai Hosp, Peritoneal Disseminat Ctr, Osaka, Japan.
    Yonemura, Yutaka
    NPO Support Peritoneal Surface Malignancy Treatme, Kyoto, Japan;Kishiwada Tokushukai Hosp, Peritoneal Disseminat Ctr, Osaka, Japan;Kusatsu Gen Hosp, Peritoneal Disseminat Ctr, Shiga, Japan.
    Levine, Edward A.
    Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA.
    Glehen, Olivier
    Hosp Civils Lyon, Ctr Hosp Univ Lyon Sud, Pierre, France.
    Goere, Diane
    Inst Gustave Roussy Canc Ctr, Villejuif, France.
    Elias, Dominique
    Inst Gustave Roussy Canc Ctr, Villejuif, France.
    Morris, David L.
    Univ New South Wales, St George Hosp, Sydney, NSW, Australia.
    Sugarbaker, Paul H.
    Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
    Tuech, Jean J.
    Ctr Hosp Rouen, Rouen, France.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Spiliotis, John D.
    Metaxa Canc Mem Hosp, Dept Surg Oncol, Piraeus, Greece.
    de Hingh, Ignace
    Catharina Hosp, Eindhoven, Netherlands.
    Ceelen, Wim
    Ghent Univ Hosp, Dept Gastrointestinal Surg, Ghent, Belgium.
    Baumgartner, Joel M.
    Univ Calif San Diego, Div Surg Oncol, Moores Canc Ctr, San Diego, CA 92103 USA.
    Piso, Pompiliu
    Krankenhaus Barmherzige Brueder Regensburg, Regensburg, Germany.
    Katayama, Kanji
    Univ Fukui, Med Sch Hosp, Canc Care Promot Ctr, Fukui, Japan.
    Deraco, Marcello
    Natl Canc Inst, Dept Surg, Milan, Italy.
    Kusamura, Shigeki
    Natl Canc Inst, Dept Surg, Milan, Italy.
    Pocard, Marc
    Hop Lariboisiere, AP HP, Paris, France.
    Quenet, Francois
    Ctr Val DAurelle, Montpellier, France.
    Fushita, Sachio
    Kanazawa Univ, Kanazawa Univ Hosp, Dept Surg, Kanazawa, Ishikawa, Japan.
    Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience2018In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 25, no 5, p. 1184-1192Article in journal (Refereed)
    Abstract [en]

    The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

  • 169.
    Lomnytska, M.
    et al.
    Karolinska Inst, Womens & Childrens Hlth, Karolinska Univ Hosp, Obstet & Gynaecol, Stockholm, Sweden..
    Stalberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Akademiska Hosp, Uppsala, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Akademiska Hosp, Uppsala, Sweden..
    Silins, Ilvars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Akademiska, Uppsala, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Akademiska Hosp, Uppsala, Sweden..
    Complications Related To Surgery For Ovarian Cancer With Intestinal Involvement2015In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 25, no 9, p. 492-492Article in journal (Other academic)
  • 170.
    Lorant, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ribbe, Ingar
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gustafsson, Ulla-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sinus Excision and Primary Closure Versus Laying Open in Pilonidal Disease: A Prospective Randomized Trial2011In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 54, no 3, p. 300-305Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical excision is the standard treatment for chronic pilonidal disease, but all excisional techniques are associated with tissue loss, risk of wound break down, and chronic healing problems. OBJECTIVE: The aim of the study was to compare sinus excision and primary closure vs a laying open technique in a prospective randomized trial. DESIGN, PATIENTS, AND INTERVENTIONS: Eighty patients were randomly assigned to sinus excision and primary closure (n = 39) or laying open (n = 41). Follow-up was performed 1, 3, and 12 months after surgery. MAIN OUTCOME MEASURE: The main outcome measure was the healing rate after 1 year. RESULTS: The healing rate was significantly higher after excision and closure than after laying open at 1 month (20 of 39 vs 8 of 41; P=.005) and 3 months (36 of 38 vs 28 of 39; P=.013) after surgery. At follow-up 12 months after surgery no difference was seen in healing rate between the treatment arms (33 of 37 vs 37 of 38; P=.198). CONCLUSIONS: This prospective randomized trial shows that sinus excision and primary closure results in faster healing than laying open does, but there is no difference in healing rate after 1 year. The laying open procedure is minimally invasive with small risks for the patient, and it might therefore be considered more frequently as the first choice of treatment (www.clinicaltrials.gov. Unique identifier: NCT00997048).

  • 171.
    Lundin, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Garske, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Segmental colonic transit studies: Comparison of a radiological and a scintigraphic method2007In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 9, no 4, p. 344-351Article in journal (Refereed)
    Abstract [en]

    Objective: Colonic transit studies are used to diagnose slow transit constipation (STC) and to evaluate segmental colonic transit before segmental or subtotal colectomy. The aim of the study was to compare a single X-ray radio-opaque marker method with a scintigraphic technique to assess total and segmental colonic transit in patients with STC. Methods: Thirty-one female patients (median age 46 years) with severe constipation and a prolonged or borderline prolonged colonic transit time on radio-opaque marker study were included in the study. They were subsequently investigated with 111 Indium-DTPA colonic transit scintigraphy, with a median time between the investigations of 4(range 1-27) months. Normal values of healthy female controls were used for comparison. Results: There was no difference between the two methods interms of prolonged or normal total colonic transit time. Twenty-nine of 31 female patients had a prolonged transit time only in one or two segments on the marker study. On scintigraphy, the transit time was prolonged for patients in the left (P < 0.05 to P < 0.001), but not in the right colon. With respect to prolonged or normal segmental transit time, there was a significant difference between the two methods only in the descending colon (P = 0.02). However, the results varied considerably for individual patients. Conclusion: Segmental colonic delay was a common finding. The two methods gave similar results for groups of patients, except in the descending colon. The variation of the results for individuals suggests that a repeated transit test may improve the assessment of total and segmental transit.

  • 172.
    Lundin, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Anorectal manovolumetry in the decision making before surgery for slow transit constipation2007In: Techniques in Coloproctology, ISSN 1123-6337, E-ISSN 1128-045X, Vol. 11, no 3, p. 259-265Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Colectomy with ileorectal anastomosis for slow transit constipation (STC) is being challenged by other operations, such as segmental resections. The importance of preoperative anorectal physiology testing may therefore be increased. The aim of this study was to identify anorectal abnormalities in patients with STC, which may influence the surgical approach. METHODS: Fifty consecutive patients with STC (43 women; median age, 49 years) and 28 controls (23 women; median age, 50 years) were examined with anorectal manovolumetry. Anal pressures and rectal volumes were recorded, at stepwise rectal distension. RESULTS: Anal resting pressure was lower in patients (median, 54 cm H(2)O; range, 22-130) than in controls (median, 68 cm H(2)O; range, 35-100) (p<0.05). Squeeze pressure tended to be lower in patients (median, 147 cm H(2)O; range, 53-382) than in controls (median, 177 cm H(2)O; range, 65-423) (p=0.09). Rectal sensory thresholds did not differ significantly between patients and controls, although 10 patients had a threshold for filling above the 95(th) percentile of controls. Rectal compliance was increased in patients in the pressure interval 5-35 cm H(2)O (p<0.05-0.01). The threshold and amplitude of the recto-anal inhibitory reflex did not differ significantly, but the recovery of resting pressure after eliciting the reflex was lower in patients than in controls in the pressure interval 10-50 cm H(2)O (p<0.05-0.001). CONCLUSIONS: More than half of the patients with STC deviated in some parameter. An impaired internal sphincter function and increased rectal compliance were seen. One fifth of the patients had impaired rectal sensation.

  • 173.
    Lundin, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Outcome of segmental colonic resection for slow-transit constipation.2002In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 89, no 10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The standard surgical treatment for slow-transit constipation (STC) is subtotal colectomy and ileorectal anastomosis. A segmental resection may serve the same purpose, but with a reduced risk of side-effects such as diarrhoea or incontinence. The aim of this study was to evaluate the functional results following segmental resection in a consecutive series of patients with STC.

    METHODS: Selection criteria included prolonged segmental transit on oral 111In-labelled diethylene triamine penta-acetic acid scintigraphic transit study, and disabling symptoms resistant to medical therapy and treatment of outlet obstruction. Twenty-eight patients (26 women, median age 52 years) were treated with segmental resection and followed prospectively with a validated questionnaire.

    RESULTS: After a median of 50 (range 16-78) months, 23 patients were pleased with the outcome. The median (range) stool frequency increased from 1 (0-7) to 7 (0-63) per week (P < 0.001). The number of patients passing hard stools and straining excessively decreased (P = 0.016 and P = 0.041, respectively). The median incontinence score was unchanged. Rectal sensory thresholds were higher in patients in whom the treatment failed (P < 0.001).

    CONCLUSION: With a symptomatic relief comparable to that after ileorectal anastomosis and less severe side-effects, segmental colectomy may be a better alternative for selected patients with STC. Thorough preoperative evaluation is important and impaired rectal sensation may predict a poor outcome.

  • 174.
    Lundin, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Westlin, Jan-Erik
    Kairemo, Kalevi
    Jung, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Husin, Stig
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Scintigraphic assessment of slow transit constipation with special reference to right- or left-sided colonic delay2004In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 6, no 6, p. 499-505Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subtotal colectomy and ileorectal anastomosis for slow transit constipation has several side-effects. The motor abnormality in some patients may be segmental which could motivate a limited resection of the colon. Therefore a diagnostic tool to identify a segmental colonic motor dysfunction is needed. The aim of this study was to evaluate a scintigraphic method to assess colonic transit with special reference to right- or left-sided delay. METHODS: Twenty-three constipated patients (19 women, mean age 50 years) with slow colonic transit on radio-opaque marker studies and 13 healthy individuals (11 women, mean age 46 years) were studied. All subjects were examined with oral (111)Indium-DTPA scintigraphy. The scintigraphic results for patients and controls were presented as geometric centre of radioactivity and percent activity over time in the right, the left and the recto-sigmoid colon. The inter-observer variation in the interpretation of the scans was also evaluated. RESULTS: There was no difference in transit time between the groups of patients and controls in the right colon whereas the patients had a significant delay in the left colon (P < 0.05). Two patients had a marked delay in the right colon followed by relatively rapid transit in the left colon. The inter-observer correlation was good comparing the right, the left and the recto-sigmoid colon (r = 0.58-0.98, P < 0.01-0.001). CONCLUSION: The results indicate that colonic scintigraphy with oral (111)Indium-DTPA may help to select patients for a left or, in a few cases, a right hemicolectomy for slow transit constipation.

  • 175.
    Magnusson, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    de Wit, Meike
    Brennan, Donal J.
    Johnson, Louis B.
    McGee, Sharon F.
    Lundberg, Emma
    Naicker, Kirsha
    Klinger, Rut
    Kampf, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wester, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gry, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bjartell, Anders
    Gallagher, William M.
    Rexhepaj, Elton
    Kilpinen, Sami
    Kallioniemi, Olli-Pekka
    Belt, Eric
    Goos, Jeroen
    Meijer, Gerrit
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Borrebaeck, Carl A. K.
    Navani, Sanjay
    Uhlen, Mathias
    O'Connor, Darran P.
    Jirstrom, Karin
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas2011In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 35, no 7, p. 937-948Article in journal (Refereed)
    Abstract [en]

    The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n = 1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.

  • 176.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, B S
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in liver metastases after intravenous and intraperitoneal administration: an autoradiographic study in the rat1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 943-949Article in journal (Refereed)
    Abstract [en]

    AIM:

    To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO) administration.

    METHODS AND RESULTS:

    A total of 18 inbred rats with hepatic metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7), i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised autoradiographically and quantified by computer-based image analysis. After 20 minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours, 9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19 i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e. injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v. injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at any time point. When the calculations were based on average metastatic radioactivity of individual rats, the difference between i.v. and i.p.e. injected rats was still present at 2 hours.

    CONCLUSION:

    These results indicate that early tumour 5-FU uptake after intraperitoneal and intraportal administration may be inferior to that after intravenous injection. Deposition of the drug in the peritoneal cavity may, however, act as a slow release preparation giving continuous drug exposure for prolonged periods of time. These results suggest a role for combined intravenous and intraperitoneal adjuvant therapy.

  • 177.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lövqvist, A
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 843-848Article in journal (Refereed)
    Abstract [en]

    Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.

  • 178.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Bengt
    Khamis, Harry
    Arow, Kiril
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat2005In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 25, no 2A, p. 917-922Article in journal (Refereed)
    Abstract [en]

    This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.

  • 179.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    von Heideman, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tholander, B.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis2008In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 34, no 5, p. 547-552Article in journal (Refereed)
    Abstract [en]

    AIMS:

    To investigate if the pattern of cytotoxic drug sensitivity in vitro in patient samples of peritoneal carcinomatosis (PC) is supportive to the current standardized approach for drug selection for perioperative intraperitoneal chemotherapy (IPC).

    METHODS:

    The cytotoxic effect of cisplatin, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin-C, doxorubicin and melphalan was investigated in vitro on tumour cells from 223 patient tumour samples of different PC origins.

    RESULTS:

    Considerable differences in cytotoxic drug sensitivity between tumour types of the PC entity and within each tumour type were observed. Cisplatin showed high cross-resistance with oxaliplatin but low cross-resistance with doxorubicin and irinotecan. No cross-resistance was found between irinotecan and doxorubicin. The dose-response relationships for melphalan and irinotecan in individual samples showed great variability.

    CONCLUSIONS:

    The activity in vitro of cytotoxic drugs commonly used in IPC for PC is very heterogeneous. Efforts for individualizing drug selection for PC patients undergoing IPC seem justified.

  • 180.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wallin, I
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ehrsson, Hans
    Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion2008In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, European Journal of Clinical Pharmacology, Vol. 64, no 9, p. 907-911Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the perfusate and systemic kinetics of oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) using a selective analytical technique. Methods HIPEC was carried out in eight patients by the open abdomen coliseum technique for 30 min at 41.5-43 degrees C with an average of 427 mg/m(2) of oxaliplatin in 5% dextrose solution. Blood and perfusate samples were collected during the perfusion. Additional blood samples were taken up to 2 h after the end of perfusion. The analysis was performed by liquid chromatography and post-column derivatization with N,N-diethyldithiocarbamate using microwave heating. Results The mean elimination half-life of oxaliplatin in the perfusate was 29.5 min (range 21.1-41.2 min) and in the peripheral circulation 24.7 min (range 21.7-27.7 min). The ratio of the areas under the time concentration curve in perfusate and blood was 12.8 +/- 2.9. Conclusion The systemic exposure of oxaliplatin measured after HIPEC using a selective analytical technique is considerably lower than previously reported results obtained by atomic absorption spectroscopy.

  • 181. Maringe, Camille
    et al.
    Walters, Sarah
    Rachet, Bernard
    Butler, John
    Fields, Tony
    Finan, Paul
    Maxwell, Roy
    Nedrebø, Bjørn
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sjövall, Annika
    Spigelman, Allan
    Engholm, Gerda
    Gavin, Anna
    Gjerstorff, Marianne L
    Hatcher, Juanita
    Johannesen, Tom B
    Morris, Eva
    McGahan, Colleen E
    Tracey, Elizabeth
    Turner, Donna
    Richards, Michael A
    Coleman, Michel P
    Stage at diagnosis and colorectal cancer survival in six high-income countries: A population-based study of patients diagnosed during 2000-20072013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 919-932Article in journal (Refereed)
    Abstract [en]

    Background

    Large international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences.

    Methods

    Data from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000-2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale.

    Results

    International differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of 'regional' disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82-84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years.

    Conclusion

    Differences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK.

  • 182.
    Martling, A.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, K. E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Olsson, H.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Granath, F.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Ekbom, A.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Risk of second primary cancer in patients treated with radiotherapy for rectal cancer2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 3, p. 278-287Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR).

    Methods: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not.

    Results: A total of 13 457 patients were included in this study; 7024 (52.2 per cent) received RT and 6433 (47.8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1.03; 95 per cent c. i. 0.92 to 1.15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1.33, 1.01 to 1.74) but not within (HR 1.11, 0.73 to 1.67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 068, 0.51 to 091).

    Conclusion: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.

  • 183. Martling, Anna
    et al.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Kodeda, Karl
    Folkesson, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    New trends in rectal cancer treatment2014In: The Open Colorectal Cancer Journal, ISSN 1876-8202, E-ISSN 1876-8202, Vol. 3, no 2, p. 215-222Article in journal (Refereed)
    Abstract [en]

    The treatment philosophy for rectal cancer has changed a lot during the last three decades. In the 1970s it was more or less a pure surgical business and rectal cancer was considered radiation resistant. Owing to the unacceptable high local recurrence rates, surgery was changed (the total mesorectal excision technique) during the 1980s and treatment was, in many countries, concentrated to lager units. Moreover, the addition of adjuvant radiotherapy was tested during the same period in several randomized trials and demonstrated that the local recurrence rate could be reduced by 50%, provided the radiation dose was high enough. Since then, treatment has changed very rapidly with several interesting approaches, such as timing and type of radiotherapy, the place of chemotherapy, surgery with modern technique including laparoscopy; natural orifice transendoscopic surgery or robotics; and the whole idea of ‘wait-and-watch’ program. All of these new aspects are covered and discussed in the view of the standard-of-care in 2014.

  • 184.
    Mayrhofer, Markus
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Kultima, Hanna Göransson
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Birgisson, Helgi
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sundström, Magnus
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Mathot, Lucy
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Edlund, Karolina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Viklund, Björn
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Sjöblom, Tobias
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Botling, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Micke, Patrick
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Påhlman, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer2014In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 872-Article in journal (Refereed)
    Abstract [en]

    Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III). Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas. Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.

  • 185. Mellgren, A.
    et al.
    Matzel, K. E.
    Pollack, J.
    Hull, T.
    Bernstein, M.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Long-term efficacy of NASHA Dx injection therapy for treatment of fecal incontinence2014In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 26, no 8, p. 1087-1094Article in journal (Refereed)
    Abstract [en]

    Background Injectable bulking treatment for fecal incontinence (FI) is intended to expand tissue in the anal canal and prevent fecal leakage. Use of injectable bulking agents is increasing because it can be performed in an outpatient setting and with low risk for morbidity. This study evaluated the long-term (36-month) clinical effectiveness and safety of injection of non-animal stabilized hyaluronic acid/dextranomer (NASHA Dx) on FI symptoms. Methods In a prospective multicenter trial, 136 patients with FI received the NASHA Dx bulking agent. Treatment success defined as a reduction in number of FI episodes by 50% or more compared with baseline (Responder(50)). Change from baseline in Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) and Fecal Incontinence Quality of Life Scale (FIQL), and adverse events were also evaluated. Key Results Successful decrease in symptoms was achieved in 52% of patients at 6 months and this was sustained at 12 months (57%) and 36 months (52%). Mean CCFIS decreased from 14 at baseline to 11 at 36 months (p < 0.001). Quality-of-life scores for all four domains improved significantly between baseline and 36 months of follow-up. Severe adverse events were rare and most adverse events were transient and pertained to minor bleeding and pain or discomfort. Conclusions & Inferences Submucosal injection of NASHA Dx provided a significant improvement of FI symptoms in a majority of patients and this effect was stable during the course of the follow-up and maintained for 3 years.

  • 186.
    Mints, Michael
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Stockholm, Sweden..
    Hiltbrunner, Stefanie
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Eldh, Maria
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Rosenblatt, Robert
    Umea Univ, Dept Surg & Perioperat Sci, Stockholm, Sweden..
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden..
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden..
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala Univ, Fac Med, Uppsala, Sweden..
    Vasko, Jonas
    Umea Univ, Dept Med Biosci, Umea, Sweden..
    Winqvist, Ola
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Stockholm, Sweden..
    Gabrielsson, Susanne
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Exosomes in urine retain a malignant protein profile after primary tumour ablation in patients with invasive urinary bladder cancer2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, p. 38-39Article in journal (Other academic)
  • 187.
    Mints, Michael
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Krantz, David
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden..
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Vasko, Jonas
    Umea Univ, Dept Med Biosci, Umea, Sweden..
    Winerdal, Malin
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Zirakzadeh, Ali
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Riklund, Katrin
    Umea Univ, Dept Radiat Sci, Umea, Sweden..
    Zubarev, Roman
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Rutishauser, Dorothea
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Winqvist, Ola
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Individual immunoproteomics identifies il-16 processing in tregs as a factor in bladder cancer tumour immunity2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no SI 220, p. 36-37Article in journal (Other academic)
  • 188. Morner, Malin E. M.
    et al.
    Gunnarsson, Ulf
    Jestin, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Svanfeldt, Monika
    The Importance of Blood Loss During Colon Cancer Surgery for Long-Term Survival: An Epidemiological Study Based on a Population Based Register2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 255, no 6, p. 1126-1128Article in journal (Refereed)
    Abstract [en]

    Objective: This study tested the hypothesis that the amount of blood loss during surgery for colonic cancer influences long-term survival.

    Background: The perioperative blood loss during surgery for colorectal cancer relates to the risk for complications and early mortality.

    Methods: All patients who underwent surgery for colon cancer between 1997 and 2003 in the health-care region of Uppsala/Orebro were prospectively registered at the regional oncological center. Data on patients who underwent radical surgery for stages I to III disease were analyzed. Patients who died within 6 months after surgery were excluded. Hazard ratios were calculated with uni- and multivariate Cox proportional hazard regression. Because of covariation, blood loss, blood transfusion, and complications were tested in separate multivariate analyses.

    Results: Blood loss of 250 mL or more during surgery, male gender, occurrence of complications, age more than 75 years, and stage III disease were risk factors for overall mortality in the uni- and multivariate analyses. Perioperative blood transfusion was shown to be a risk factor in the univariate analysis only.

    Conclusions: The results support the hypothesis that degree of blood loss during surgery for colon cancer is a factor that influences long-term survival.

  • 189. Morner, Malin
    et al.
    Gunnarsson, Ulf
    Jestin, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Egenvall, Monika
    Volume of blood loss during surgery for colon cancer is a risk determinant for future small bowel obstruction caused by recurrence-a population-based epidemiological study2015In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 400, no 5, p. 599-607Article in journal (Refereed)
    Abstract [en]

    Small bowel obstruction (SBO) is a serious late complication after abdominal surgery. The pathogenesis of intra-abdominal adhesions has been extensively studied and reviewed, but the cascade of mechanisms involved is still not understood. The objective was to test the hypothesis that increasing volume of blood loss during surgery for colon cancer increases the risk for future SBO, mainly due to adhesions. Data were retrieved from the Regional Quality Register for all patients undergoing locally radical surgery for colon cancer 1997-2003 (n = 3 554) and matched with the Swedish National Patient Register data on surgery and admission for SBO. Records were reviewed to determine the etiology of surgery for SBO. Uni- and multivariate Cox analyses were used. One hundred ten patients (3.1 %) underwent surgery for SBO > 30 days after the index operation. Blood loss a parts per thousand yen250 ml was an independent risk factor for surgery for SBO due to recurrence (HR 2.20; 95 % CI 1.12-4.31). Amount of blood loss did not affect the risk for surgery for SBO due to adhesions. Furthermore, blood loss of a parts per thousand yen250 ml increased the risk for hospital admission for SBO not requiring surgery. Blood loss a parts per thousand yen250 ml during surgery for colon cancer is an independent risk factor for later surgery for SBO caused by tumor recurrence, not by adhesions.

  • 190. Morris, Arden M.
    et al.
    Delaney, Conor P.
    Påhlman, Lars A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Phang, P. Terry
    Canadian Association of General Surgeons, the American College of Surgeons, the Canadian Society of Colorectal Surgeons, and the American Society of Colorectal Surgeons Evidence Based Reviews in Surgery: Colorectal Surgery2012In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 55, no 10, p. 1096-1098Article in journal (Other academic)
  • 191. Morris, Eva J. A.
    et al.
    Sandin, Fredrik
    Lambert, Paul C.
    Bray, Freddie
    Klint, Asa
    Linklater, Karen
    Robinson, David
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Moller, Henrik
    A population-based comparison of the survival of patients with colorectal cancer in England, Norway and Sweden between 1996 and 20042011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no 8, p. 1087-1093Article in journal (Refereed)
    Abstract [en]

    Objective To examine differences in the relative survival and excess death rates of patients with colorectal cancer in Norway, Sweden and England. Methods All individuals diagnosed with colorectal cancer (ICD10 (International Classification of Diseases, 10th revision) C18-C20) between 1996 and 2004 in England, Norway and Sweden were included in this population-based study of patients with colorectal cancer. The main outcome measures were 5-year cumulative relative period of survival and excess death rates stratified by age and period of follow-up. Results The survival of English patients with colorectal cancer was significantly lower than was observed in both Norway and Sweden. Five-year age-standardised colon cancer relative survival was 51.1% (95% CI 50.1% to 52.0%) in England compared with 57.9% (95% CI 55.2% to 60.5%) in Norway and 59.9% (95% CI 57.7% to 62.0%) in Sweden. Five-year rectal cancer survival was 52.3% (95% CI 51.1% to 53.5%) in England compared with 60.7% (95% CI 57.0% to 64.2%) and 59.8% (95% CI 56.9% to 62.6%) in Norway and Sweden, respectively. The lower survival for colon cancer in England was primarily due to a high number of excess deaths among older patients in the first 3 months after diagnosis. In patients with rectal cancer, excess deaths remained elevated until 2 years of follow-up. If the lower excess death rate in Norway applied in the English population, then 890 (13.6%) and 654 (16.8%) of the excess deaths in the colon and rectal cancer populations, respectively, could have been prevented at 5 years follow-up. Most of these avoidable deaths occurred shortly after diagnosis. Conclusions There was significant variation in survival between the countries, with the English population experiencing a poorer outcome, primarily due to a relatively higher number of excess deaths in older patients in the short term after diagnosis. It seems likely, therefore, that in England a greater proportion of the population present with more rapidly fatal disease (especially in the older age groups) than in Norway or Sweden.

  • 192. Mroczkowski, Paweł
    et al.
    Ortiz, Hector
    Penninckx, Freddy
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    European quality assurance programme in rectal cancer: are we ready to launch?2012In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 8, p. 960-966Article in journal (Refereed)
    Abstract [en]

    Aim: 

    There have been initiatives to create a European audit project. This paper addresses the issue of differences in data collected by different registries.

    Method:

    Patients with rectal cancer treated in 2008 and recorded in quality registries from Belgium, Germany/Poland, Spain and Sweden were analysed. The comparison included number of patients, gender, age, ASA-classification, preoperative diagnostic and staging procedures, neoadjuvant therapy, surgical treatment and quality of surgery, postoperative complications, and adjuvant treatment.

    Results: 

    The Belgian database consisted of 622 patients, Germany/Poland 3,393, Spain 1,641 and Sweden 1,826. The percentage of patients in ASA-stages was highly variable.MRI-use was the highest in Spain and Sweden and very low in Germany/Poland. The percentage of cT4 stage tumours in Sweden was much higher than in all other countries. Sweden recorded the highest percentage of primary metastatic disease (20.3%), Belgium the lowest (10.2%). Neoadjuvant therapy in different protocols was administered to 41.2% patients in Germany/Poland, 50.8% in Spain, 55.2% in Belgium and 62% in Sweden.Laparoscopic surgery (conversion rate) was performed for cure in 5% (28%) of patients in Sweden, in 20.8% (20.6%) in Spain, in 28.6% (15.2%) in Belgium and in 14.5% (8.9%) in Germany/Poland.30 day mortality for anterior resection, abdominoperineal resection and Hartmann's procedure in Sweden, Belgium and Spain 2.0%, 2.3% and 3.1%, respectively. The German-Polish database reported an in-hospital mortality of 3.2%.

    Conclusion: 

    A European quality assurance project in rectal cancer is possible only after data collection is standardised.