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  • 1. Adam, René
    et al.
    de Gramont, Aimery
    Figueras, Joan
    Kokudo, Norihiro
    Kunstlinger, Francis
    Loyer, Evelyne
    Poston, Graeme
    Rougier, Philippe
    Rubbia-Brandt, Laura
    Sobrero, Alberto
    Teh, Catherine
    Tejpar, Sabine
    Van Cutsem, Eric
    Vauthey, Jean-Nicolas
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus2015In: Cancer Treatment Reviews, ISSN 0305-7372, E-ISSN 1532-1967, Vol. 41, no 9, p. 729-741Article in journal (Refereed)
    Abstract [en]

    An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.

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  • 2.
    Andréasson, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    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.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve2013In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 8, p. 930-936Article in journal (Refereed)
    Abstract [en]

    Background: Cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy is a highly invasive treatment of peritoneal metastasis and requires many surgical procedures before mastering. The aim of this study was to estimate how many procedures are needed before stabilization can be seen in surgical outcome (R1 surgery, adverse events and bleeding) in patients with pseudomyxoma peritonei (PMP). Patients and methods: All 128 patients with PMP who were treated with CRS alone or CRS plus perioperative intraperitoneal chemotherapy between 2003 and 2008 at the Uppsala University Hospital, Uppsala, Sweden, were included. The learning curve was calculated using the partial least square (PLS) and cumulative sum control chart (CUSUM) graph. Two groups were formed based on the results of the learning curve. The learning curve plateau was considered the same as the stabilization in the CUSUM graph. Group I consisted of patients included during the learning period (n = 73) and Group 11 of patients treated after the learning period ended (n = 55). Comparisons between the groups were made on surgical outcome, survival and adverse events. Results: Stabilization was seen after 220 +/- 10 procedures. A higher occurrence of R1 surgery was seen in Group H (80%) compared to Group I (48%; P = 0.0002). Overall survival increased at four years after surgery in Group H compared to Group I (80% vs. 63%; P = 0.02). Conclusion: CRS plus perioperative intraperitoneal chemotherapy is a highly demanding procedure that requires more than 200 procedures before optimisation in surgical outcome is seen.

  • 3.
    Andréasson, Håkan
    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.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The natural history of pseudomyxoma peritonei- the early phaseManuscript (preprint) (Other academic)
  • 4.
    Andréasson, Sara Näslund
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Anundi, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sahlberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ericsson, Claes-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wålinder, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Enlund, G.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles2008In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 35, no 7, p. 780-784Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3cm from the breathing area of the surgeon (personal sampling) and 3m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1mum. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3x10(6)particle/ml/h (pt/ml/h)) than in the control group (4.8x10(5)pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6x10(6) pt/ml/h) than in the control group (3.9x10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.

  • 5. Arbman, Gunnar
    et al.
    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 Radiology, Oncology and Radiation Science, Oncology.
    The rise and fall of a longed for clinical trial in patients with generalized colorectal cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, p. 1779-1782Article in journal (Refereed)
  • 6.
    Augestad, Knut M.
    et al.
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Lindsetmo, Rolv-Ole
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Stulberg, Jonah
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Reynolds, Harry
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Senagore, Anthony
    Spectrum Health Care, Department of Surgery, Michigan State University, USA.
    Champagne, Brad
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Heriot, Alexander G.
    Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
    Leblanc, Fabien
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Delaney, Conor P.
    Division of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, USA.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    International preoperative rectal cancer management: staging, neoadjuvant treatment, and impact of multidisciplinary teams2010In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 34, no 11, p. 2689-2700Article in journal (Refereed)
    Abstract [en]

    Background

    Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates.

    Methods

    One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer.

    Results

    One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years’ experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventyfour percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p= 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p= 0.0001), MRI for all RC patients (20% vs. 42%, p= 0.03), and ERUS for all RC patients (43% vs. 21%, p= 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR =5.67, stage II + III RR =2.98), quality of pathology report (RR= 4.85), and sphincter-saving surgery (RR = 3.81).

    Conclusions

    There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods. 

  • 7.
    Berglund, Ake
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nygren, Peter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pahlman, Lars
    Department of Surgical Sciences. Gastrointestinal Surgery.
    Sundin, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    [Limit investigation in cancer of unknown primary site]2005In: Lakartidningen, ISSN 0023-7205, Vol. 102, no 41, p. 2946-8, 2950Article in journal (Other scientific)
  • 8.
    Birgisson, H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy2008In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 95, no 2, p. 206-13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the study was to analyse late gastrointestinal disorders necessitating hospital admission following rectal cancer surgery and to determine their relationship to preoperative radiation therapy. METHODS: Curatively treated patients participating in the Swedish Rectal Cancer Trial during 1987-1990, randomized to preoperative irradiation (454 patients) or surgery alone (454), were matched against the Swedish Hospital Discharge Registry. Hospital records for patients admitted with gastrointestinal diagnoses were reviewed. RESULTS: Irradiated patients had an increased relative risk (RR) of late small bowel obstruction (RR 2.49 (95 per cent confidence interval (c.i.) 1.48 to 4.19)) and abdominal pain (RR 2.09 (95 per cent c.i. 1.03 to 4.24)) compared with patients treated by surgery alone. The risk of late small bowel obstruction requiring surgery was greatly increased (RR 7.42 (95 per cent c.i. 2.23 to 24.66)). Irradiated patients with postoperative anastomotic leakage were at increased risk for late small bowel obstruction (RR 2.99 (95 per cent c.i. 1.07 to 8.31)). The risk of small bowel obstruction was also related to the radiation technique and energy used. CONCLUSION: Small bowel obstruction is more common in patients with rectal cancer treated with preoperative radiation therapy.

  • 9.
    Birgisson, H
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Talbäck, M
    Gunnarsson, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, B
    Department of Oncology, Radiology and Clinical Immunology.
    Improved survival in cancer of the colon and rectum in Sweden.2005In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 31, no 8, p. 845-53Article in journal (Refereed)
  • 10.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wallin, Ulrik
    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.
    Kultima, Hanna Göransson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mayrhofer, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, article id 125Article in journal (Refereed)
    Abstract [en]

    Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.

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  • 11.
    Birgisson, Helgi
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 34, p. 8697-705Article in journal (Refereed)
  • 12.
    Birgisson, Helgi
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Occurrence of second cancers in patients treated with radiotherapy for rectal cancer.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 25, p. 6126-31Article in journal (Refereed)
  • 13.
    Birgisson, Helgi
    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.
    Gunnarsson, Ulf
    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.
    Late adverse effects of radiation therapy for rectal cancer: a systematic overview2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 4, p. 504-516Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. METHODS: Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5 x 5 Gy radiation therapy with surgery alone. RESULTS: The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. CONCLUSIONS: These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.

  • 14. Bonjer, H. Jacob
    et al.
    Hop, Wim C. J.
    Nelson, Heidi
    Sargent, Daniel J.
    Lacy, Antonio M.
    Castells, Antoni
    Guillou, Pierre J.
    Thorpe, Helen
    Brown, Julia
    Delgado, Salvadora
    Kuhrij, Esther
    Haglind, Eva
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Laparoscopically assisted vs open colectomy for colon cancer: a meta-analysis2007In: Archives of surgery (Chicago. 1960), ISSN 0004-0010, E-ISSN 1538-3644, Vol. 142, no 3, p. 298-303Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe. DATA SOURCES: The databases of the Barcelona, Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection (COLOR), and Conventional vs Laparoscopic-Assisted Surgery in Patients With Colorectal Cancer (CLASICC) trials were the data sources for the study. STUDY SELECTION: Patients who had at least 3 years of complete follow-up data were selected. DATA EXTRACTION: Patients who had undergone curative surgery before March 1, 2000, were studied. Three-year disease-free survival and overall survival were the primary outcomes of this analysis. DATA SYNTHESIS: Of 1765 patients, 229 were excluded, leaving 796 patients in the laparoscopically assisted arm and 740 patients in the open arm for analysis. Three-year disease-free survival rates in the laparoscopically assisted and open arms were 75.8% and 75.3%, respectively (95% confidence interval [CI] of the difference, -5% to 4%). The associated common hazard ratio (laparoscopically assisted vs open surgery with adjustment for sex, age, and stage) was 0.99 (95% CI, 0.80-1.22; P = .92). The 3-year overall survival rate after laparoscopic surgery was 82.2% and after open surgery was 83.5% (95% CI of the difference, -3% to 5%). The associated hazard ratio was 1.07 (95% CI, 0.83-1.37; P = .61). Disease-free and overall survival rates for stages I, II, and III evaluated separately did not differ between the 2 treatments. CONCLUSION: Laparoscopically assisted colectomy for cancer is oncologically safe.

  • 15.
    Breugom, A. J.
    et al.
    Leiden Univ, Med Ctr, Surg, Leiden, Netherlands..
    Bastiaannet, E.
    Leiden Univ, Med Ctr, Surg, Leiden, Netherlands..
    Boelens, P. G.
    Leiden Univ, Med Ctr, Surg, Leiden, Netherlands..
    Van Eycken, E.
    Belgian Canc Registry, Res, Brussels, Belgium..
    Vandendael, T.
    Belgian Canc Registry, Res, Brussels, Belgium..
    Iversen, L. H.
    Aarhus Univ Hosp, Surg, DK-8000 Aarhus, Denmark..
    O'Brien, K.
    Natl Canc Registry Ireland, Res, Cork, Ireland..
    Martling, A.
    Karolinska Inst, Moleculare Med & Surg, Stockholm, Sweden..
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Liefers, G. J.
    Leiden Univ, Med Ctr, Surg, Leiden, Netherlands..
    Rutten, H. J. T.
    Catharina Hosp, Surg, Eindhoven, Netherlands..
    Lemmens, V. E.
    Comprehens Canc Ctr Netherlands, Res, Utrecht, Netherlands..
    Van de Velde, C. J. H.
    Leiden Univ, Med Ctr, Surg, Leiden, Netherlands..
    Differences in proportion adjuvant chemotherapy are not associated with relative survival for stage II colon cancer patients aged 75 years and older - a EURECCA international comparison2015In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no S3, p. S195-S195Article in journal (Other academic)
  • 16. Breugom, A. J.
    et al.
    van Gijn, W.
    Muller, E. W.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    van den Broek, C. B. M.
    Fokstuen, T.
    Gelderblom, H.
    Kapiteijn, E.
    Leer, J. W. H.
    Marijnen, C. A. M.
    Martijn, H.
    Kranenbarg, E. Meershoek-Klein
    Nagtegaal, I. D.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Punt, C. J. A.
    Putter, H.
    Roodvoets, A. G. H.
    Rutten, H. J. T.
    Steup, W. H.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    van de Velde, C. J. H.
    Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 4, p. 696-701Article in journal (Refereed)
    Abstract [en]

    Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo) radiotherapy and total mesorectal excision (TME). Patients and methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1: 1) to observation or adjuvant chemotherapy after preoperative (chemo) radiotherapy and TME. Radiotherapy consisted of 5 x 5 Gy. Chemoradiotherapy consisted of 25 x 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo) radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.

  • 17. Ceelen, Wim P.
    et al.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pharmacodynamic aspects of intraperitoneal cytotoxic therapy2007In: Cancer treatment and research, ISSN 0927-3042, Vol. 134, p. 195-214Article in journal (Refereed)
    Abstract [en]

    The rationale for ip administration as an adjunct to surgery is firmly based on theoretical and pharmacokinetic grounds. The superiority of combined ip and intravenous chemotherapy over intravenous chemotherapy alone has been established in randomized trials in stage IIIc ovarian cancer patients. Intraoperative ip cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption. At present, however, it is not clearly established to what extent this PK advantage will result in enhanced anticancer activity and, ultimately, in a survival benefit. Preclinical models show that direct penetration into tumour tissue is limited to a few millimeters. Furthermore, the limited exposure time of intraoperative chemoperfusion could limit cytotoxic activity despite high local concentrations. Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia. Newer agents such as the taxanes and the camptothecins appear promising for ip chemoperfusion during or immediately after surgery. Pharmacodynamic aspects of HIPEC needing further preclinical study-including mathematical modeling - are the establishment of tumour tissue penetration of the newer agents and its relation to hyperthermia, the definition of the relative contribution of direct penetration versus vascular supply by absorbed drug, and the efficacy of combined ip and intravenous regimens. Ultimately, however, randomised trials of ip chemotherapy with surgery will have to provide the evidence base to further build upon.

  • 18.
    Chabok, Abbas
    et al.
    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.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hjern, F.
    Haapaniemi, S.
    Smedh, Kennet
    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.
    Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis2012In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 4, p. 532-539Article in journal (Refereed)
    Abstract [en]

    Background: The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up.

    Methods: This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics.

    Results: Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1.9 per cent) who received no antibiotics and in three (1.0 per cent) who were treated with antibiotics (P = 0.302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0.881).

    Conclusion: Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis.

  • 19.
    Chabok, Abbas
    et al.
    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.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 20.
    Collin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gustafsson, Ulla-Maria
    Smedh, Kenneth
    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.
    Folkesson, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The effect of local gentamicin-collagen on perineal wound complications and cancer recurrence after abdominoperineal resection: a multicentre randomised controlled trial2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 3, p. 341-346Article in journal (Refereed)
    Abstract [en]

    Aim: 

    Perineal wound sepsis is a common problem after abdominoperineal resection of the rectum (APR), with an reported incidence of 10-15% in previously non-radiated patients, 20-30% in patients given preoperative radiation, and 50% among patients submitted to preoperative radiation combined with chemotherapy. The local application of gentamicin-collagen was evaluated to determine whether its use in the perineal wound reduced the risk complications and had an effect on cancer recurrence.

    Method: 

    In this prospective multicentre (7 hospitals) randomised controlled trial, 102 patients undergoing APR due to cancer or benign disease were randomised into two groups including surgery with gentamicin-collagen (GS+ n=52), or surgery without gentamicin-collagen (GS- n=50), Patients were followed at 7, 30 and 90 days and at one and five years.

    Results: 

    There were no statistically significant differences between the two groups regarding perineal wound complications, infectious or non-infectious or cancer recurrence.

    Conclusion: 

    There was no statistically significant effect on perineal wound complications or cancer recurrence following the local administration of gentamicin-collagen during APR.

  • 21.
    Collin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jung, B.
    Nilsson, E.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Folkesson, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Impact of mechanical bowel preparation on survival after colonic cancer resection2014In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 101, no 12, p. 1594-1600Article in journal (Refereed)
    Abstract [en]

    Background: A randomized study in 1999-2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. Methods: The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. Results: Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17.9 per cent) of 448 patients in the MBP group and 88 (22.5 per cent) of 391 in the no-MBP group developed a cancer recurrence (P = 0.093). The 10-year cancer-specific survival rate was 84.1 per cent in the MBP group and 78.0 per cent in the no-MBP group (P = 0.019). Overall survival rates were 58.8 and 56.0 per cent respectively (P = 0.186). Conclusion: Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years.

  • 22.
    Dafnis, G
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Granath, F
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ekbom, A
    Blomqvist, P
    Patient factors influencing the completion rate in colonoscopy.2005In: Dig Liver Dis, ISSN 1590-8658, Vol. 37, no 2, p. 113-8Article in journal (Refereed)
  • 23.
    Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The Use of Pre- or Postoperative Antibiotics in Surgery for Appendicitis: A Systematic Review2014In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 103, no 1, p. 14-20Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: The aim of this study was to review the literature regarding the use of pre- and/or postoperative antibiotics in the management of appendicitis, using data obtained from PubMed and the Cochrane Library.

    MATERIAL AND METHODS: A literature search was conducted using the terms "appendicitis" combined with "antibiotics." Studies were selected based on relevance for the evidence on prophylactic and postoperative treatment with regard to the route and duration of drug administration and the findings of surgery.

    RESULTS: Patients with acute appendicitis should receive preoperative, broad-spectrum antibiotics. The use of postoperative antibiotics is only recommended in cases of perforation, and treatment should then be given intravenously, for a minimum period of 3-5 days for adult patients, until clinical signs such as fever resolve and laboratory parameters such as C-reactive protein curve and white blood cell (WBC) start to decline.

    CONCLUSION: Preoperative antibiotic prophylaxis is recommended in all patients with acute appendicitis, whereas postoperative antibiotics only in cases of perforation.

  • 24.
    Deijen, Charlotte L.
    et al.
    Vrije Univ Amsterdam.
    Vasmel, Jeanine E.
    Vrije Univ Amsterdam.
    de Lange-de Klerk, Elly S. M.
    Vrije Univ Amsterdam.
    Cuesta, Miguel A.
    Vrije Univ Amsterdam.
    Coene, Peter-Paul L. O.
    Maasstad Hosp, Rotterdam, Netherlands..
    Lange, Johan F.
    Erasmus MC, Rotterdam, Netherlands..
    Meijerink, W. J. H. Jeroen
    Vrije Univ Amsterdam.
    Jakimowicz, Jack J.
    Delft Univ Technol.
    Jeekel, Johannes
    Erasmus MC, Dept Surg, Rotterdam.
    Kazemier, Geert
    Vrije Univ Amsterdam.
    Janssen, Ignace M. C.
    Rijnstate Hosp, Dept Surg, Arnhem.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Haglind, Eva
    Sahlgrens Univ Hosp.
    Bonjer, H. Jaap
    Vrije Univ Amsterdam.
    Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer2017In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 31, no 6, p. 2607-2615Article in journal (Refereed)
    Abstract [en]

    Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

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  • 25. D'Hoore, A.
    et al.
    Albert, M. R.
    Cohen, S. M.
    Herbst, F.
    Matter, I.
    Van der Speeten, K.
    Dominguez, J.
    Rutten, H.
    Muldoon, J. P.
    Bardakcioglu, O.
    Senagore, A. J.
    Ruppert, R.
    Mills, S.
    Stamos, M. J.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Choman, E.
    Wexner, S. D.
    COMPRES: a prospective postmarketing evaluation of the compression anastomosis ring CAR 27/ColonRing2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 6, p. 522-529Article in journal (Refereed)
    Abstract [en]

    AimPreclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing in (low) colorectal anastomosis. MethodThe primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained. ResultsBetween 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses. ConclusionNitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing with conventional stapling is needed.

  • 26. Djureinovic, Tatjana
    et al.
    Lindblom, Annika
    Dalén, Johan
    Dedorson, Stefan
    Edler, David
    Hjern, Fredrik
    Holm, Jörn
    Lenander, Claes
    Lindforss, Ulrik
    Lundqvist, Nils
    Olivecrona, Hans
    Olsson, Louise
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rutegård, Jörgen
    Smedh, Kennet
    Törnqvist, Anders
    Eiberg, Hans
    Bisgaard, Marie Luise
    The CHEK2 1100delC variant in Swedish colorectal cancer2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 6C, p. 4885-4888Article in journal (Refereed)
    Abstract [en]

    Background: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. Patients and Methods: To evaluate the role of CHEK2 1100delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in 18 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. Results: CHEK2 1100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. Conclusion: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.

  • 27. Egenvall, M.
    et al.
    Morner, M.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunnarsson, U.
    Degree of blood loss during surgery for rectal cancer: a population-based epidemiologic study of surgical complications and survival2014In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 16, no 9, p. 696-702Article in journal (Refereed)
    Abstract [en]

    Aim The hypothesis tested in this study was that major blood loss during surgery for rectal cancer increases the risk for surgical complications and for small bowel obstruction (SBO) as a result of adhesions or tumour recurrence, and reduces overall survival. Method Data were retrieved from the Uppsala/Orebro Regional Rectal Cancer Registry for all patients undergoing radical resection for rectal cancer during 1997-2003 (n = 1843) and were matched against the Swedish National Patient Registry regarding surgery and admission for SBO. These patient records were scrutinized to determine the etiology of surgery for SBO. The registry was scrutinized for blood loss and other surgical complications associated with surgery. Uni- and multivariate Cox analysis and logistic regression were used. Results Ninety-four (5.1%) patients underwent surgery for SBO > 30 days after the index operation: 82 for adhesions and 12 for tumour recurrence. The volume of blood lost did not influence the risk of surgery for SBO as a result of adhesions, but blood loss above the median (>= 800 ml) increased the risk for surgery for SBO caused by tumour recurrence (hazard ratio = 10.52; 95% CI: 1.36-81.51). Increased blood loss increased the risk of surgical complications (OR = 1.78; 95% CI: 1.35-2.35 with blood loss of >= 450 ml) but did not reduce overall survival. Irradiation before surgery increased blood loss, complications and admission for SBO. Conclusion Major blood loss during surgery for rectal cancer increases the risk of later surgery for SBO caused by tumour recurrence and surgical complications, but overall survival is not affected.

  • 28.
    Enroth, Stefan
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Rada-Iglesisas, Alvaro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Andersson, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wallerman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pahlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Komorowski, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wadelius, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. 450-Article in journal (Refereed)
    Abstract [en]

    Background: Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Methods: Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. Results: By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. Conclusions: Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers.

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  • 29. Fleming, Fergal J.
    et al.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Monson, John R. T.
    Neoadjuvant Therapy in Rectal Cancer2011In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 54, no 7, p. 901-912Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The optimal type of neoadjuvant therapy regimen in rectal cancer is contentious. OBJECTIVE: This study aimed to review the impact of neoadjuvant therapy on oncological outcomes and complications (short and long term) in patients undergoing total mesorectal excision for rectal cancer. DATA SOURCES: An electronic search of MEDLINE, PubMed, EMBASE, and the Cochrane Database of Collected Reviews was performed through March 2010. STUDY SELECTION: Key-word combinations including rectal cancer, total mesorectal excision, radiotherapy, chemotherapy, endorectal ultrasound, and magnetic resonance imaging were used to identify randomized control trials where chemotherapy and/or radiotherapy were deployed before resectional surgery. INTERVENTION(S): Patients underwent total mesorectal excision for rectal cancer who did and did not receive preoperative chemotherapy and/or radiotherapy. MAIN OUTCOME MEASURES: The main outcome measures comprised the impact of the addition of neoadjuvant therapy to total mesorectal excision on the perioperative complication rate, the pathological complete response rate, the rate of local recurrence, and long- term treatment-related complications. RESULTS: A total of 12 randomized control trials involving 9410 patients were included. Both short-course radiotherapy and long-course chemoradiation can offer a relative risk reduction of 50% in local recurrence in appropriately selected patients with stage II and III rectal cancer. This oncological benefit comes at the cost of a relative risk increase of 50% in both acute treatment-related toxicity and long-term anorectal dysfunction. LIMITATIONS: Preoperative staging provides only an estimate of the "true" tumor stage that can only be determined by histological assessment of the tumor specimen which renders appropriate patient selection challenging. CONCLUSIONS: The current treatment trade-off of a relative risk reduction of local recurrence of 50% at the cost of a relative increase of 50% in treatment-related complications underpins the need for more accurate patient staging and more precise delivery of neoadjuvant therapy.

  • 30.
    Folkesson, J
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, J
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, B
    Department of Oncology, Radiology and Clinical Immunology.
    Gunnarsson, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    The circular stapling device as a risk factor for anastomotic leakage.2004In: Colorectal Dis, ISSN 1462-8910, Vol. 6, no 4, p. 275-9Article in journal (Refereed)
  • 31.
    Folkesson, Joakim
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Cedermark, Bjorn
    Glimelius, Bengt
    Department of Oncology, Radiology and Clinical Immunology. ONK.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 24, p. 5644-50Article in journal (Refereed)
  • 32.
    Folkesson, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Brown, Steven S R
    Gunnarsson, Ulf
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Randomised multicentre trial of circular stapling devices2012In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 27, no 2, p. 227-232Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    In a register study, the risk of anastomotic leakage correlated to the choice of circular stapling device with a 4% difference between the two brands used. Based on those data, a randomised multicentre study was started to explore the risk of an anastomotic leakage based upon the surgical device.

    METHODS:

    Patients above 18 years with a rectal cancer, able to give informed consent, and scheduled for an anterior resection were eligible for the study. Perioperative randomisation was to Ethicon™ PROXIMATE™ ILS™ or Autosuture™ Premium Plus CEEA™. Anastomotic leakage was defined as a clinically manifest leak.

    RESULTS:

    Five hundred twenty-nine patients were randomised (58% male). A leak occurred in 8.3%. The anastomoses created by PROXIMATE™ ILS™ leaked in 25/265 (9.4%) anastomoses, and the Premium Plus CEEA™ leaked in 19/260 (7.3%), p = .419.

    CONCLUSION:

    No difference in the leak rate could be revealed. Several centres replaced one of the staplers by a new product, and the study was ended before the stipulated number of patients was reached. In the future, surgical devices may have to prove superiority in randomised trials or be monitored in quality registers before they can be introduced into day to day surgical practice.

  • 33.
    Folkesson, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Robert
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Population-based study of local surgery for rectal cancer2007In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 94, no 11, p. 1421-1426Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to determine long-term survival and recurrence rates after local excision of rectal cancer from a prospectively registered population-based database. Methods: Swedish Rectal Cancer Registry data from 1995 to 2001, including 10181 patients of whom 643 (6-3 per cent) had a local excision, were analysed. Complete 5-year follow-up data from 1995 to 1998 were available. Cumulative relative and cancer-specific survival rates, and rates of local recurrence and distant metastases, were calculated by actuarial methods. Results: The 5-year cancer-specific survival rate for 256 patients with stage I disease who had local excision was 95-3 (95 per cent confidence interval 91-5 to 99-1) per cent. The 5-year local recurrence rate was 7-2 per cent. After adjustment for age, sex, tumour stage and preoperative radiotherapy, the relative risk of death from cancer was the same as that after major resection. Conclusion: Population-based results after local excision of rectal cancer are the same as those reported in controlled series for early-stage tumours after abdominal resection. A low relative survival and a high median age indicate the use of local excision in patients with a high level of co-morbidity. To achieve acceptable long-term results, optimal preoperative and postoperative staging is needed.

  • 34.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Darmanis, Spyros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Detection of prognostic biomarkers with solid-phase proximity ligation assay in patients with colorectal cancer2016In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 9, no 3, p. 251-255Article in journal (Refereed)
    Abstract [en]

    Background: In the search for prognostic biomarkers a significant amount of precious biobanked blood samples is needed if conventional analyses are used. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyse many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of  SP-PLA in patients with colorectal cancer (CRC).

    Material and methods: Plasma from patients with stage I-IV CRC, with (n=31) and without (n=29) disease dissemination at diagnosis or later, was analysed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5 ml plasma. Carcinoembryonic antigen (CEA), analysed earlier on this cohort, was used as a reference.

    Results: A total of 21 of the 35 proteins were detectable with SP-PLA. Patients in stage II-III with disseminated disease had lower plasma concentrations of HCC-4 (p=0.025). Low plasma levels of TIMP-1 were seen in patients with disseminated disease stage II (p=0.003). The level of CEA was higher in patients with disease dissemination compared to those without (p=0.007).

    Conclusion: SP-PLA has the ability to analyse many tumour markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information compared with CEA. 

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  • 35.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Lund Univ, Div Oncol Pathol, Dept Clin Sci, Lund, Sweden..
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 2, p. 311-321Article in journal (Refereed)
    Abstract [en]

    Background: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives.

    Material and methods: Tumour tissues from 320 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases.

    Results: Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p= 1.000). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p= 0.006) and prolonged time to recurrence (p= 0.040). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 3.87; CI, 1.36-11.01). The same prognostic information was potentially also in distal colon cancer; no recurrences seen in the 8 patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant.  Conclusion:No correlation between MSI and heredity was seen. Patients with MSI tumours had improved survival.

     

  • 36. Ghazi, Sam
    et al.
    von Holst, Susanna
    Picelli, Simone
    Lindforss, Ulrik
    Tenesa, Albert
    Farrington, Susan M
    Campbell, Harry
    Dunlop, Malcolm G
    Papadogiannakis, Nikos
    Lindblom, Annika
    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.
    Colorectal cancer susceptibility loci in a population-based study: associations with morphological parameters2010In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 177, no 6, p. 2688-2693Article in journal (Refereed)
    Abstract [en]

    Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.

  • 37.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Beets-Tan, Regina
    Blomqvist, Lennart
    Brown, Gina
    Nagtegaal, Iris
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quirke, Phil
    Valentini, Vincenzo
    van de Velde, Cornelis
    Mesorectal Fascia Instead of Circumferential Resection Margin in Preoperative Staging of Rectal Cancer2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 16, p. 2142-2143Article in journal (Other academic)
  • 38. Glimelius, Bengt
    et al.
    Dahl, Olav
    Cedermark, Björn
    Jakobsen, Anders
    Bentzen, Sören M
    Starkhammar, Hans
    Grönberg, Henrik
    Hultborn, Ragnar
    Albertsson, Maria
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Tveit, Kjell-Magne
    Adjuvant chemotherapy in colorectal cancer: A joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.2005In: Acta Oncol, ISSN 0284-186X, Vol. 44, no 8, p. 904-12Article in journal (Refereed)
  • 39.
    Grevfors, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Torkzad, Michael R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Can acute abdominal CT prioritise patients with suspected diverticulitis for a subsequent clean colonic examination?2012In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 7, p. 893-896Article in journal (Refereed)
    Abstract [en]

    Aim: 

    The aim of this study was to investigate whether patients with diverticulitis can be prioritised with higher urgency for a subsequent full colonic examination based upon the emergency abdominal computerised tomography (CT) at the time of presentation.

    Method:

    All patients with a diagnosis of diverticulitis hospitalized during 2006 having CT on admission and a subsequent 'clean colon' examination were reviewed. The CT was reviewed by two independent and blinded senior radiologists (A and B) for signs inconsistent with diverticulitis and suggestive of malignancy. The patients were classified on CT into group 1 (normal findings, non-tumour pathology or benign polyps < 1 cm) and group 2 (benign polyps ≥ 1 cm and cancer).

    Results: 

    93 patients were reviewed with 83 in group 1and 10 in group 2. Radiologist A suggested high priority colonic examination in 18% and 50% of groups 1 and 2, and Radiologist B in 63% and 90%. There was a statically significant inter-observer difference and also lower accuracy of Radiologist B than Radiologist A in predicting a subsequent 'clean colon' examination.

    Conclusion: 

    Using an emergency acute CT scan at the time of diagnosis of diverticulitis to predict a clean colon examination for neoplasia is not reliable since there is considerable degree of inter-observer difference between rediologista.

  • 40.
    Gunnarsson, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Karlbom, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Docker, M
    Raab, Y
    Pahlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Proctocolectomy and pelvic pouch--is a diverting stoma dangerous for thepatient?2004In: Colorectal Dis, Vol. 6, p. 23-Article in journal (Refereed)
  • 41.
    Gurmu, Ambatchew
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Matthiessen, Peter
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Rutegård, Jörgen
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The inter-observer reliability is very low at clinical examination of parastomal hernia2011In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 26, no 1, p. 89-95Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Parastomal hernia in patients with a permanent colostomy is common. The aim of this study was to evaluate the reliability of the diagnosis based on clinical examination and to compare this examination with the result of a specially designed questionnaire and computerised tomography (CT) scan. METHODS: Forty-one patients operated upon with an abdominoperineal resection due to rectal cancer at three hospitals between 1996 and 2002 were included. At minimum of 4 years after the operation, they underwent clinical examination by two or three independent surgeons, answered a colostomy questionnaire and were offered a CT scan of the abdominal wall. RESULT: At Hospital I, 17 patients were examined by three surgeons, with inter-observer kappa values between 0.35 and 0.64. At Hospital II, 13 patients were examined by three surgeons, the kappa values ranged between 0.29 and 0.43. At Hospital III, 11 patients were examined by two surgeons, with kappa value of 0.73. The kappa value between CT scan and the colostomy questionnaire was 0.45. CONCLUSION: The inter-observer reliability was low, indicating that parastomal hernia is difficult to diagnose by patient history and clinical examination. Some herniae may not be detected by CT scan, and the correlation to patient-reported complaints is low. A more sensitive radiological method to detect parastomal hernia is needed.

  • 42. Hakama, Matti
    et al.
    Hoff, Geir
    Kronborg, Ole
    Påhlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Screening for colorectal cancer.2005In: Acta Oncol, ISSN 0284-186X, Vol. 44, no 5, p. 425-39Article in journal (Refereed)
  • 43.
    Hall, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Blom, Elisabeth
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Ulin, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Monazzam, Azita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    McBride, William
    Goldenberg, David M
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting2012In: American journal of nuclear medicine and molecular imaging, ISSN 2160-8407, Vol. 2, no 2, p. 141-150Article in journal (Refereed)
    Abstract [en]

    The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with 67Ga or 68Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of 67/68Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using 67Ga and SPECT or 68Ga and PET.

  • 44.
    Hansson, Johan
    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.
    Påhlman, Lars
    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.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Postoperative adverse events and long-term survival after cytoreductive surgery and intraperitoneal chemotherapy2009In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 35, no 2, p. 202-208Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Peritoneal carcinomatosis (PC) is fatal without special combined cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). This study was designed to identify factors that may increase the risk of postoperative morbidity and mortality from combined CRS and IPC interventions for PC. Survival based on primary tumour type and extent of surgery is reported. METHODS: Between May 1991 and November 2004, 123 patients were treated with CRS and IPC for PC. Based on the National Cancer Institute Common Toxicity Criteria for grade 3 and 4, data on 30 days postoperative morbidity and 90 days mortality were analysed. RESULTS: Grade 3-4 adverse events were observed in 51 patients (41%) and were associated with stoma formation, duration of surgery, peroperative blood loss and peritoneal cancer index (PCI). Excision, or electrocautery evaporation, of tumour from small bowel surface was correlated to bowel morbidity. Five patients had treatment-related mortality (4%) within 90 days. Survival was associated with macroscopic radical surgery, prior surgical score, PCI and primary tumour type. CONCLUSIONS: CRS and IPC for PC are associated with high morbidity and mortality. However, in light of the potential benefit indicated by long-term survival, the adverse event from this treatment is considered acceptable.

  • 45.
    Hassan, Saadia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Laryea, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Felth, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Fayad, Walid
    Linder, Stig
    Rickardson, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gullbo, Joachim
    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.
    Pålman, 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 Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Novel activity of acriflavine against colorectal cancer tumor cells2011In: Cancer Science, ISSN 1347-9032, E-ISSN 1349-7006, Vol. 102, no 12, p. 2206-2213Article in journal (Refereed)
    Abstract [en]

    A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.

  • 46. Heald, Richard
    et al.
    Moran, Brendan
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Christensen, Henrik Kidmose
    Optimering af kirurgi ved rectumcancer: [Optimising surgery for rectal cancer]2011In: Ugeskrift for læger, ISSN 1603-6824, Vol. 173, no 14, p. 1044-1047Article in journal (Refereed)
    Abstract [en]

    The crucial aspect of open as well as laparoscopic rectal cancer surgery is to find the correct dissection plane to avoid damage of the nerves and to create a perfect specimen. By doing so, a "specimen oriented" resection will be achieved and the risk of a positive circumferential resection margin minimized. Currently, and for the foreseeable future, open surgery remains optimal for complex cases and in cases where a low difficult restorative resection is needed. Optimal surgery remains a crucial part in the curative treatment of this technically challenging cancer.

  • 47.
    Hesselager, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Vuong, Té
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Richard, Carole
    Liberman, Sender
    Letellier, François
    Folkesson, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Short-term outcome after neoadjuvant high-dose-rate endorectal brachytherapy or short-course external beam radiotherapy in resectable rectal cancer2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 6, p. 662-666Article in journal (Refereed)
    Abstract [en]

    AIM:

    Total mesorectal excision with preoperative radiotherapy reduces local recurrence in rectal cancer, but radiotherapy increases the risk of complications. The study compared the immediate postoperative outcome after external beam radiotherapy with high dose endorectal brachytherapy (HDREBT).

    METHOD:

    Patients (n=318) treated with preoperative HDREBT, (26 Gy over 4 days) followed by surgery after 4-8 weeks were matched with 318 patients from the Swedish Rectal Cancer Register treated with 5 Gy daily over 5 days and surgery in the subsequent week (SCRT) and 318 having surgery alone. All 954 patients were followed for 30 days after surgery. Complications were divided into surgical, cardiovascular and infectious.

    RESULTS:

    The SCRT group had fewer cardiovascular complications (3.1%) than HDREBT (9.4%, p=0.002) and RT- (7.2%, p=0.03). Perioperative bleeding was less in HDREBT patients (379.3 ml) than SCRT (947.2 ml; p<0.0001) and RT- (918.9 ml), and the re-intervention rate was lower in HDREBT (4.1%) than SCRT patients (14.2%; p=0.005) and RT- (12.3%; p<0.005). The HDREBT group had fewer R2 resections than the SCRT and RT- groups, but a higher proportion of R0-resections than the RT- group (p=0.03).

    CONCLUSION:

    No major differences in postoperative complications were found. HDREBT patients had a higher rate of cardiovascular complications but less perioperative bleeding and fewer re-interventions. A longer interval between radiotherapy and surgery may be beneficial for tumour regression and this could be reflected in the number of radical resections.

  • 48.
    Hosseinali Khani, Maziar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Treatment strategies for patients with stage IV rectal cancer: a report from the Swedish Rectal Cancer Registry2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no 11, p. 1616-1623Article in journal (Refereed)
    Abstract [en]

    Background: The optimal treatment strategy for patients with stage IV rectal cancer is unclear. The aim of the present study was to describe trends and compare the different treatment strategies for this group of patients at a national level and over time.

    Methods: Data from 2758 rectal cancer patients with (stage IV group) and 13 420 without metastases (stage I-III group) were available from the Swedish Rectal Cancer Registry between January 1995 and December 2006.

    Results: Patients with stage IV disease increased from 15 to 19 per cent between 1995 and 2006 (p<0.001) and the frequency of patients not operated increased from 13 to 26 per cent (p<0.001). Postoperative 30 day mortality after bowel resection was 2 per cent and after exploratory laparotomy 9 per cent. Median survival for stage IV patients operated with bowel resection was 16.3 months, an exploratory laparotomy 6.1 months, and for patients having no surgery 4.6 months. Patients aged 60-69 years increased their survival over time, irrespective of the treatment given. In the multivariate analysis, an increased risk of death was associated with: age > 80 years, operation at a local hospital, treatment in earlier time periods, not receiving preoperative radio- or chemotherapy, and not having a bowel resection.

    Conclusion: Survival for stage IV rectal cancer patients improved in the latest time period despite the great increase in non-operated patients. Patients aged > 80 years should be carefully assessed and staged before surgery. The survival advantage for stage IV rectal cancer patients who underwent primary tumour resection is probably due to selection bias.

  • 49.
    Jestin, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Heurgren, M
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Elective surgery for colorectal cancer in a defined Swedish population.2004In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 30, no 1, p. 26-33Article in journal (Refereed)
  • 50.
    Jestin, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Gunnarsson, Ulf
    Department of Medical Cell Biology.
    Cancer staging and survival in colon cancer is dependent on the quality of the pathologists' specimen examination.2005In: Eur J Cancer, ISSN 0959-8049, Vol. 41, no 14, p. 2071-8Article in journal (Other scientific)
1234 1 - 50 of 152
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