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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.

  • 2.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Dubois, Noemie
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tradivel, Isabelle
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Haavik, Jan
    Husebye, Eystein
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Meloni, Antonella
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Vilattes, Bernard
    Kajosaari, Merja
    Egner, William
    Sargur, Ravishankar
    Amoura, Zahir
    Grimfeld, Alain
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    De Luca, Filippo
    Betterle, Corrado
    Perheentupa, Jaakko
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 11, p. 4396-4401Article in journal (Refereed)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  • 3. Andersson, Magnus V.
    et al.
    Andersson, Peter
    Bohe, Måns
    Börjesson, Lars
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jeppsson, Bengt
    Törkvist, Leif
    Åkerlund, Jan-Erik
    Söderholm, Johan Dabrosin
    Kirurgi – omistligt komplement till medicinsk behandling2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 3003-9Article in journal (Refereed)
    Abstract [sv]

    Kirurgi på rätt indikation och vid rätt tidpunkt är ett omistligt komplement till medicinsk behandling vid inflammatorisk tarmsjukdom, som förebygger sjukdomskomplikationer, förbättrar patienternas livskvalitet och ibland är livräddande. Kirurgi för ulcerös kolit görs oftast som ett tvåstegsförfarande: först kolektomi plus ileostomi med rektum lämnad intakt och i senare skede, med optimerad patient, tarmrekonstruktion anpassad efter patientens individuella livssituation. Kirurgi vid Crohns sjukdom korrigerar komplikationer (stenoser och fistlar) och sparar tarm genom begränsade resektioner och strikturplastiker. Laparoskopisk kir­urgi verkar ha viktiga fördelar vid primära tarmresektioner. Modern medicinsk behandling har förändrat indikationerna men ännu inte minskat behovet av kirurgi. Pågående antiinflammatorisk och immunmodulerande behandling är viktig att beakta i samband med kirurgi. Ett nära samspel mellan gastroenterolog och kolorektalkirurg är nödvändigt för att uppnå bästa möjliga långtidsprognos för de individer som lever med IBD.

  • 4.
    Andreasson, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Sun, Xiao-Feng
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Zhang, Zhi-Yong
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1443-1448Article in journal (Refereed)
    Abstract [en]

    Aim:

    The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.

    Materials and Methods:

    Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.

    Results:

    The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).

    Conclusion:

    The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.

  • 5.
    Andréasson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pseudomyxoma Peritonei: Aspects of Natural History, Learning Curve, Treatment Outcome and Prognostic Factors2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous peritoneal metastasis (PM). Different loco-regional treatment strategies, i.e. debulking surgery and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), have changed the prognosis for these patients. CRS is an aggressive surgical procedure with a long learning curve. PMP exists in different types; how many depends on which classification is used.

    The aims of this thesis were to investigate the time-frame of PMP development from an isolated appendiceal neoplasm, examine the learning process for CRS, evaluate the differences in treatment outcome between debulking surgery and CRS in combination with HIPEC, to evaluate a more detailed PMP classification and to investigate particularly interesting new cysteine-histidine (PINCH) protein as a prognostic factor for PMP.

    Retrospectively 26 PMP patients were identified as having had an appendectomy with a neoplasm in the appendix but with no evidence of PM at the appendectomy. They were treated for PMP within a median of 13.1 months (3.8-95.3) after the appendectomy. No difference was seen between the types of PMP regarding the time to a clinically significant development of PMP and how much tumour was found at treatment. CRS is a highly invasive treatment and stabilization in the learning curve was seen after 220±10 procedures. Patients treated with CRS+HIPEC had a better 5-year overall survival (OS) than patients treated with debulking surgery, 74% vs. 40%. CRS increased the rate of complete cytoreduction from 25% in patients treated with debulking surgery to 72%. The new four-grade PMP classification showed very good inter-rater agreement between two independent pathologists and a difference in survival rates was observed between the different grades. A positive PINCH staining was recorded in 83% of the tumours and that was associated with poorer survival.

    List of papers
    1. The natural history of pseudomyxoma peritonei- the early phase
    Open this publication in new window or tab >>The natural history of pseudomyxoma peritonei- the early phase
    (English)Manuscript (preprint) (Other academic)
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-197430 (URN)
    Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2013-08-30
    2. Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
    Open this publication in new window or tab >>Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
    Show others...
    2013 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 8, p. 930-936Article in journal (Refereed) Published
    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.

    Keywords
    Cytoreductive surgery; Pseudomyxoma peritonei; Learning curve; Survival
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-197433 (URN)10.1016/j.ejso.2014.03.001 (DOI)000339533700004 ()24656455 (PubMedID)
    Funder
    Swedish Cancer Society, 10-0561 CAN 2010/569
    Available from: 2013-04-08 Created: 2013-03-25 Last updated: 2017-12-06Bibliographically approved
    3. Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
    Open this publication in new window or tab >>Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
    Show others...
    2012 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, p. 962-968Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.

    PATIENTS AND METHODS:

    Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.

    RESULTS:

    One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).

    CONCLUSIONS:

    CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-181434 (URN)10.1016/j.ejso.2012.07.009 (DOI)000309787600012 ()22809859 (PubMedID)
    Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
    4. Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
    Open this publication in new window or tab >>Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
    Show others...
    2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1443-1448Article in journal (Refereed) Published
    Abstract [en]

    Aim:

    The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.

    Materials and Methods:

    Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.

    Results:

    The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).

    Conclusion:

    The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.

    Keywords
    Pseudomyxoma peritonei, histopathology, PINCH, protein expression, cytokeratin 7, Ki-67
    National Category
    Medical and Health Sciences Basic Medicine
    Research subject
    Pathology
    Identifiers
    urn:nbn:se:uu:diva-173640 (URN)000302492600043 ()22493383 (PubMedID)
    Available from: 2012-05-09 Created: 2012-05-02 Last updated: 2018-01-12Bibliographically approved
  • 6.
    Andréasson, Håkan
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, p. 962-968Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.

    PATIENTS AND METHODS:

    Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.

    RESULTS:

    One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).

    CONCLUSIONS:

    CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.

  • 7.
    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.

  • 8.
    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)
  • 9.
    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.

  • 10.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Defining operating room efficiency from the perspective of the staff member and the supervisor2011In: International Journal for Quality in Health Care, ISSN 1353-4505, E-ISSN 1464-3677, Vol. 23, no 3, p. 220-221Article in journal (Refereed)
  • 11.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    How operating room efficiency is understood in a surgical team: a qualitative study2011In: International Journal for Quality in Health Care, ISSN 1353-4505, E-ISSN 1464-3677, Vol. 23, no 1, p. 100-106Article in journal (Refereed)
    Abstract [en]

    Objective. Building surgical teams is one attempt to ensure the health-care system becomes more efficient, but how is 'efficiency'understood or interpreted? The aim was to study how organized surgical team members and their leaders understood operating room efficiency.

    Design. Qualitative study.

    Settings. A 1100-bed Swedish university hospital.

    Participants. Eleven participants, nine team members from the same team and their two leaders were interviewed.

    Methods. The analysis was performed according to phenomenography, a research approach that aims to discover variationsin peoples' understanding of a henomenon.

    Results. Seven ways of understanding operating room efficiency were identified: doing one's best from one's prerequisites,enjoying work and adjusting it to the situation, interacting group performing parallel tasks, working with minimal resources to produce desired results, fast work with preserved quality, long-term effects for patient care and a relative concept. When talking about the quality and benefits of delivered care, most team members invoked the patient as the central focus. Despite seven ways of understanding efficiency between the team members, they described their team as efficient. The nurses and assistant nurses were involved in the production and discussed working in a timely manner more than the leaders.

    Conclusions. The seven ways of understanding operating room efficiency appear to represent both organization-oriented andindividual-oriented understanding of that concept in surgical teams. The patient is in focus and efficiency is understood as maintaining quality of care and measuring benefits of care for the patients.

  • 12.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Job satisfaction or production? How staff and leadership understand operating room efficiency: a qualitative study2008In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 10, p. 1423-1428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: How to increase efficiency in operating departments has been widely studied. However, there is no overall definition of efficiency. Supervisors urging staff to work efficiently may meet strong reactions due to staff believing that demands for efficiency means just stress at work. Differences in how efficiency is understood may constitute an obstacle to supervisors' efforts to promote it. This study aimed to explore how staff and leadership understand operating room efficiency. METHODS: Twenty-one members of staff and supervisors in an operating department in a Swedish county hospital were interviewed. The analysis was performed with a phenomenographic approach that aims to discover the variations in how a phenomenon is understood by a group of people. RESULTS: Six categories were found in the understanding of operation room efficiency: (A) having the right qualifications; (B) enjoying work; (C) planning and having good control and overview; (D) each professional performing the correct tasks; (E) completing a work assignment; and (F) producing as much as possible per time unit. The most significant finding was that most of the nurses and assistant nurses understood efficiency as individual knowledge and experience emphasizing the importance of the work process, whereas the supervisors and physicians understood efficiency in terms of production per time unit or completing an assignment. CONCLUSIONS: The concept 'operating room efficiency' is understood in different ways by leadership and staff members. Supervisors who are aware of this variation will have better prerequisites for defining the concept and for creating a common platform towards becoming efficient.

  • 13.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Norlén, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Factors influencing early postoperative recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy2011In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 37, no 10, p. 897-903Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can prolong survival in selected patients with peritoneal carcinomatosis (PC). However, there is little data on patients' recovery process after this complex treatment. This study aimed to describe the in-hospital postoperative recovery and factors related to the recovery of patients who undergo CRS and HIPEC.

    METHOD:

    A retrospective audit of the electronic health record (EHR) was undertaken for 76 PC patients (42 women, 34 men) treated primarily with CRS and HIPEC between 2005 and 2006 in Sweden.

    RESULTS:

    Oral intake, regaining bowel functions and mobilisation usually occurred between 7 and 11 days postoperatively. Patients experienced nausea for up to 13 days postoperatively. Forty-two patients were satisfied with their pain management, which usually took the form of epidural anaesthesia and which continued for about one week post-surgery. Sleep disturbance was observed in 51 patients and psychological problems in 49 patients during the first three postoperative weeks. Tumour burden, stoma formation, use of CPAP, primary diagnosis, and the length of stay in the ICU were factors related to an early recovery process.

    CONCLUSION:

    Drinking, eating, regaining bowel functions and mobilisation were re-established within 11 days of CRS and HIPEC. Tumour burden, stoma formation, use of CPAP, primary diagnosis and the length of stay in the ICU all had an impact on postoperative recovery, and should be discussed with the patients preoperatively and taken into consideration in designing an individualised patient care plan, in order to attain a more efficient recovery.

  • 14.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    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.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pulmonary influences on early postoperative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment2011In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598Article in journal (Other academic)
  • 15.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    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.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: a retrospective study2012In: World Journal of Surgical Oncology, ISSN 1477-7819, E-ISSN 1477-7819, Vol. 10, p. 258-Article in journal (Refereed)
    Abstract [en]

    Background: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. Methods: Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Results: Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1-2) in nine patients. Conclusions: Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.

  • 16. 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)
  • 17.
    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. 

  • 18.
    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.

  • 19.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ghanipour, Arezo
    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.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    The correlation between a family history of colorectal cancer and survival of patients with colorectal cancer2009In: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 8, no 4, p. 555-561Article in journal (Refereed)
    Abstract [en]

    The purpose was to analyze survival of patients with colorectal cancer and a positive family history for colorectal cancer in first degree relatives compared with those with no such family history and to determine whether differences in survival could be explained by known clinico-pathological factors. During 2000-2003, 318 consecutive patients with colorectal cancer answered a written questionnaire about their family history for colorectal cancer. During a 6-year follow-up, recurrences and survival were registered. Thirty-one (10%) patients had a first-degree relative with colorectal cancer, moreover two patients fulfilled the criteria of hereditary non-polyposis colorectal cancer and were excluded. Patients with a first-degree relative with colorectal cancer had better survival and lower risk for recurrences compared to those with no relatives with colorectal cancer. In a multivariate analysis including age, gender, stage of disease, tumor differentiation, vascular invasion and family history, patients with first-degree relatives with colorectal cancer had lower risks for death (RR 0.37; 95% CI 0.17-0.78) and death from cancer (RR 0.25; 95% CI 0.08-0.80), compared to those with a no relative with colorectal cancer. The differences were seen in patients with colon cancer but not rectal cancer. Family history for colorectal cancer in a first-degree relative is an individual prognostic factor in patients with colon cancer and could not be explained by known clinico-pathological factors. The value of family history taking in patients with colon cancer is therefore not only to identify families with hereditary colorectal cancer, but also to add information to the prognosis of the patients.

  • 20.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Stenman, Ulf-Håkan
    Serum concentrations of human chorionic gonadotropin beta and its association with survival in patients with colorectal cancer2012In: CANCER BIOMARK, ISSN 1574-0153, Vol. 11, no 4, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Increased serum concentrations of the beta subunit of human chorionic gonadotropin (hCG beta) are associated with adverse prognosis in several cancers. The aim of the present study was to analyse the association between serum hCG beta recurrence, and survival, in patients with colorectal cancer. The concentrations of hCG beta were determined in serum collected preoperatively from 324 patients with colorectal cancer, of whom 270 were curatively treated. The serum concentrations of hCG beta were associated with increasing age and they were higher in women than in men. Using the 75th percentile (1.55 pmol/L) as a cut-off for serum hCG beta, overall survival (OS) was shorter in patients with elevated concentrations (HR 1.95; 95% CI 1.39-2.74; P = 0.004), and this association was stronger in women (P = 0.022) than in men (P = 0.061). In multivariate analyses including age, disease stage, tumour differentiation, vascular invasion and CEA, high serum hCG beta concentrations remained an independent prognostic factor for adverse OS in women (HR 2.26; 95% CI 1.39-3.67), but not in men (HR 0.78; 95% CI 0.41-1.51). The same trend was observed for disease free-and cancer specific survival. High serum concentration of hCG beta is an independent prognostic factor for adverse outcome in women with colorectal cancer.

  • 21.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nielsen, Hans J.
    Christensen, Ib Jarle
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Brünner, Nils
    Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: a prospective validation study2010In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 46, no 18, p. 3323-3331Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC. Patients and methods: During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms. Results: High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels. Conclusions: This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.

  • 22.
    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, U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, B.
    Authors' reply: Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy (Br J Surg 2008; 95 : 206-213)2008In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 95, no 6, p. 803-803Article in journal (Refereed)
  • 23.
    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.

  • 24.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wallin, Ulrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. 438-Article in journal (Refereed)
    Abstract [en]

    Background: In cancer research the selection and definitions of survival endpoints are important and yet they are not used consistently. The aim of this study was to compare different survival endpoints in patients with primary colorectal cancer (CRC) and to understand the effect of second primary other cancer on disease-free survival (DFS) calculations.

    Methods: A population-based cohort of 415 patients with CRC, 332 of whom were treated with curative intention between the years 2000-2003, was analysed. Events such as locoregional recurrence, distant metastases, second primary cancers, death, cause of death and loss to follow-up were recorded. Different survival endpoints, including DFS, overall survival, cancer-specific survival, relapse-free survival, time to treatment failure and time to recurrence were compared and DFS was calculated with and without inclusion of second primary other cancers.

    Results: The events that occurred most often in patients treated with curative intention were non-cancer-related death (n = 74), distant metastases (n = 66) and death from CRC (n = 59). DFS was the survival endpoint with most events (n = 170) followed by overall survival (n = 144) and relapse-free survival (n = 139). Fewer events were seen for time to treatment failure (n = 80), time to recurrence (n = 68) and cancer-specific survival (n = 59). Second primary other cancer occurred in 26 patients and its inclusion as an event in DFS calculations had a detrimental effect on the survival. The DFS for patients with stage I-III disease was 62% after 5 years if second primary other cancer was not included as an event, compared with 58% if it was. However, the difference was larger for stage II (68 vs 60%) than for stage III (49 vs 47%).

    Conclusions: The inclusion of second primary other cancer as an endpoint in DFS analyses significantly alters the DFS for patients with CRC. Researchers and journals must clearly define survival endpoints in all trial protocols and published manuscripts.

  • 25.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Andreasson, Håkan
    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.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei2015In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 22, p. S810-S816Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic drugs, we investigated the basis for IPC drug selection and the role of IPC in the management of PMP.

    METHODS: Tumor cells were prepared by collagenase digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was correlated to progression-free survival (PFS) and overall survival (OS).

    RESULTS: Samples from 92 patients were analyzed successfully. Drug sensitivity varied considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly more resistant to platinum and 5FU and tumor cells from patients previously treated with chemotherapy were generally less sensitive than those from untreated patients. Multivariate analysis showed patient performance status and completeness of CRS to be prognostic for OS. Among patients with complete CRS (n = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin (p ≈ 0.06). At the highest drug concentration tested, the hazard ratio for disease relapse increased stepwise with drug resistance for all drugs.

    CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic information. The results suggest a role for IPC as therapeutic adjunct to CRS and for individualization of IPC by pretreatment assessment of drug sensitivity.

  • 26.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pseudomyxoma Peritone: symptoms, treatment, prognosis and sensitivity to cytostatic drugs in vitro2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, no S159, p. 71-71Article in journal (Other academic)
  • 27.
    Blom, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Yin, Li
    Liden, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dolk, Anders
    Jeppsson, Bengt
    Pahlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nyren, Olof
    Toward understanding non participation in sigmoidoscopy screening for colorectal cancer2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 122, no 7, p. 1618-1623Article in journal (Refereed)
    Abstract [en]

    Understanding the reasons for nonparticipation in cancer screening may give clues about how to improve compliance. However, limited cooperation has hampered research on nonparticipant profiles. We took advantage of Sweden's comprehensive demographic and health care registers to investigate characteristics of all participants and nonparticipants in a pilot program for colorectal cancer screening with sigmoidoscopy. A population-based sample of 1986 Swedish residents 59-61 years old was invited. Registers provided information on each individual's gender, country of birth, marital status, education, income, hospital contacts, place of residence, distance to screening center and cancer within the family. Odds ratios (ORs) with 95% confidence intervals (CIs), modeled with multivariable logistic regression, estimated the independent associations between each background factor and the propensity for nonparticipation after control for the effects of other factors. All statistical tests were 2-sided. Being male (OR = 1.27, 95% CI = 1.03-1.57, relative to female), unmarried or divorced (OR = 1.69, 95% CI = 1.23-2.30 and OR = 1.49, 95% CI = 1.14-1.95, respectively, relative to married) and having an income in the lowest tertile (OR = 1.68, 95% CI = 1.27-2.23, relative to highest tertile) was associated with increased nonparticipation. Living in the countryside or in small communities and having a documented family history of colorectal cancer was associated with better participation. Distance to the screening center did not significantly affect participation, nor did recent hospital care consumption or immigrant status. To increase compliance, invitations must appeal to men, unmarried or divorced people and people with low socioeconomic status.

  • 28.
    Blom, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Yin, Li
    Lidén, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dolk, Anders
    Jeppsson, Bengt
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nyrén, Olof
    A 9-year follow-up study of participants and nonparticipants in sigmoidoscopy screening: importance of self-selection2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 5, p. 1163-1168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Self-selection may compromise cost-effectiveness of screening programs. We hypothesized that nonparticipants have generally higher morbidity and mortality than participants. METHODS: A Swedish population-based random sample of 1,986 subjects ages 59 to 61 years was invited to sigmoidoscopy screening and followed up for 9 years by means of multiple record linkages to health and population registers. Gender-adjusted cancer incidence rate ratio (IRR) and overall and disease group-specific and mortality rate ratio (MRR) with 95% confidence intervals (95% CI) were estimated for nonparticipants relative to participants. Cancer and mortality rates were also estimated relative to the age-matched, gender-matched, and calendar period-matched Swedish population using standardized incidence ratios and standardized mortality ratios. RESULTS: Thirty-nine percent participated. The incidence of colorectal cancer (IRR, 2.2; 95% CI, 0.8-5.9), other gastrointestinal cancer (IRR, 2.7; 95% CI, 0.6-12.8), lung cancer (IRR, 2.2; 95% CI, 0.8-5.9), and smoking-related cancer overall (IRR, 1.4; 95% CI, 0.7-2.5) tended to be increased among nonparticipants relative to participants. Standardized incidence ratios for most of the studied cancers tended to be >1.0 among nonparticipants and <1.0 among participants. Mortality from all causes (MRR, 2.4; 95% CI, 1.7-3.4), neoplastic diseases (MRR, 1.9; 95% CI, 1.1-3.5), gastrointestinal cancer (MRR, 4.7; 95% CI, 1.1-20.7), and circulatory diseases (MRR, 2.3; 95% CI, 1.2-4.2) was significantly higher among nonparticipants than among participants. Standardized mortality ratio for the studied outcomes tended to be increased among nonparticipants and was generally decreased among participants. CONCLUSION: Individuals who might benefit most from screening are overrepresented among nonparticipants. This self-selection may attenuate the cost-effectiveness of screening programs on a population level.

  • 29.
    Bolin, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hansson, Agneta
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Histidine-Rich Glycoprotein as an Early Biomarker of Preeclampsia2011In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 4, p. 496-501Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prediction of preeclampsia is of great interest and the coagulation system as well as the angiogenic pathway is known to be dysfunctional in preeclampsia. Histidine-rich glycoprotein (HRG) is a protein interacting with both these biological systems and the purpose of this prospective, longitudinal cohort study was to analyze whether there is a difference in circulating levels of HRG during pregnancy in women developing preeclampsia compared to normal healthy pregnancies. We furthermore wanted to evaluate whether HRG has the potential of being an early biomarker of preeclampsia. METHODS: A cohort of healthy pregnant women (n = 469) was enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37 and analyzed with an enzyme-linked immunosorbent assay. RESULTS: The levels of HRG decreased during pregnancy in all women, but the levels were significantly lower at gestational weeks 10, 25, and 28 in women who later developed preeclampsia than in normal pregnant women (P < 0.05, P < 0.05, and P < 0.05). CONCLUSION: Our data indicates that HRG levels in plasma might be a possible biomarker already in gestational week 10 for prediction of later onset of preeclampsia in a low risk population.

  • 30. 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.

  • 31. Braendengen, Morten
    et al.
    Tveit, Kjell M.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Birkemeyer, Elke
    Frykholm, Gunilla
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wiig, Johan N.
    Byström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Bujko, Krzysztof
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 22, p. 3687-3694Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. PATIENTS AND METHODS: The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). RESULTS: The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. CONCLUSION: CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

  • 32.
    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)
  • 33. 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.

  • 34.
    Brännstrom, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Jestin, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Matthiessen, P.
    Gunnarsson, U.
    Degree of Specialisation of the Surgeon Influences Lymph Node Yield after Right-Sided Hemicolectomy2013In: Digestive Surgery, ISSN 0253-4886, E-ISSN 1421-9883, Vol. 30, no 4-6, p. 362-367Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the degree to which specialisation or case-load of the surgeon is associated with the number of lymph nodes isolated from pathology specimens after right-sided hemicolectomy. Method: Data from 6 hospitals with well-defined catchment areas included in the Uppsala/Orebro Regional Oncology Centre Colon Cancer Register 1997-2006 were used to assess 821 patients undergoing right-sided hemicolectomy for stages I Ill colon cancer. Factors influencing the lymph node yield were evaluated. Results: A surgeon with colorectal accreditation and a university pathology department were both associated with a significantly higher proportion of patients having 12 or more lymph nodes isolated from surgical specimens after right-sided hemicolectomy in both unadjusted and multivariate analyses. Emergency surgery did not affect the lymph node yield. Conclusion: The degree of specialisation of the surgeon influences the number of lymph nodes isolated from specimens obtained during routine right-sided colon cancer surgery.

  • 35.
    Brännström, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Jestin, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Matthiessen, P.
    Gunnarsson, U.
    Surgeon and hospital-related risk factors in colorectal cancer surgery2011In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 13, no 12, p. 1370-1376Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to identify surgeon and hospital-related factors in a well-defined populationbased cohort; the results of this study could possibly be used to improve outcome in colorectal cancer.

    Method: Data from the colonic (1997-2006) and rectal (1995-2006) cancer registers of the Uppsala/Orebro Regional Oncology Centre were used to assess 1697 patients with rectal and 2692 with colonic cancer. Putative risk factors and their impact on long-term survival were evaluated using the Cox proportional hazard model.

    Results: The degree of specialization of the operating surgeon had no significant effect on long-term survival. When comparing the surgeons with the highest degree of specialization, noncolorectal surgeons demonstrated a slightly lower long-term survival for rectal cancer stage I and II (HR, 2.03; 95% CI, 1.05-3.92). Surgeons with a high case-load were not associated with better survival in any analysis model. Regional hospitals had a lower survival rate for rectal cancer stage III surgery (HR, 1.47; 95% CI, 1.08-2.00).

    Conclusion: Degree of specialization, surgeon case-load and hospital category could not be identified as important factors when determining outcome in colorectal cancer surgery in this study.

  • 36. Buunen, Mark
    et al.
    Veldkamp, Ruben
    Hop, Wim C. J.
    Kuhry, Esther
    Jeekel, Johannes
    Haglind, Eva
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cuesta, Miguel A.
    Msika, Simon
    Morino, Mario
    Lacy, Antonio
    Bonjer, Hendrik J.
    Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial2009In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 10, no 1, p. 44-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. METHODS: Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. FINDINGS: During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). INTERPRETATION: Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

  • 37. Cao, Christopher
    et al.
    Yan, Tristan D.
    Morris, David L.
    van der Speeten, Kurt
    Laurberg, Soren
    Glehen, Olivier
    Link, Karl
    Piso, Pompiliu
    Tentes, Antonios-Apostolos K.
    Deraco, Marcello
    Larsen, Stein G.
    Kecmanovic, Dragutin
    Bayon, Luis G.
    Melero, Juan T.
    Gonzalez-Moreno, Santiago
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gertsch, Philippe
    Moran, Brendan
    Esquivel, Jesus
    Alexander, Richard
    Levine, Edward A.
    Sugarbaker, Paul H.
    Prospective Registry On Mesothelioma Peritonei Treatment (PROMPT): study design and rationale2012In: Tumori (Milano), ISSN 0300-8916, E-ISSN 2038-2529, Vol. 98, no 1, p. 166-171Article in journal (Refereed)
    Abstract [en]

    Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive and rare form of cancer arising from the mesothelial lining of the peritoneum. Due to the latency period between asbestos exposure and disease progression, the peak in incidence of DMPM is likely to occur in the coming decade for many industrialized nations, with a multitude of industrial, medico-legal and health-related implications(1,2). Traditional therapeutic modalities such as systemic chemotherapy and radiotherapy have not been proven to be effective in the treatment of DMPM, and patients diagnosed with the disease have a life expectancy of less than 12 months(3-5). Combined treatment involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been utilized in several specialized centers around the world and has been found to be a feasible procedure with encouraging survival outcomes(6-8).

  • 38.
    Cashin, Peter
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Considerations on the Selection Process for Cytoreductive Surgery and Hyperthermic IntraPeritoneal Chemotherapy for Colorectal Carcinomatosis Reply2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 262, no 2, p. e48-e49Article in journal (Refereed)
  • 39.
    Cashin, Peter H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer: Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity 2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperthermic intraperitoneal chemotherapy-HIPEC vs. sequential postoperative intraperitoneal chemotherapy-SPIC) and choice of drugs for IPC were the aspects covered in this thesis.

    The treatment outcome of CRS and IPC according to the median overall survival ranged from 24 to 34 months with 5-year overall survival ranging from 20 to 40% depending on the IPC treatment administered. Furthermore, the 5-year disease-free survival was impressive at 32% for patients receiving HIPEC. This establishes the curative potential of this treatment. Due to current inadequacies of radiological imaging, a score (Corep score) was developed for patient selection purposes. This score had a sensitivity of 80% and specificity of 100% in identifying patients with short cancer-specific survival after the treatment (<12 months). Further studies are needed to elucidate the clinical usefulness of the Corep score. HIPEC was associated with better survival than the SPIC method at similar morbidity and mortality rates, suggesting that HIPEC be the method of preference. Concerning the choice of drugs, the last study investigated the chemo-sensitivity of different PM tumour-types with a special focus on CRC. While CRC samples were generally more resistant, the ratio of the in vivo concentration compared to the ex vivo concentration giving a 50% tumour cell death showed that oxaliplatin had the best profile across all PM tumour types as well as for CRC. This needs further confirmation in a clinical trial.

    List of papers
    1. Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    Open this publication in new window or tab >>Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    2012 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed) Published
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

    Keywords
    HIPEC, Intraperitoneal chemotherapy, Colorectal cancer, Peritoneal carcinomatosis, Cytoreductive surgery, Recurrences
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169544 (URN)10.1016/j.ejso.2012.03.001 (DOI)000304510600008 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    2. Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    Open this publication in new window or tab >>Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    2012 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed) Published
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

    Keywords
    colorectal cancer, corep score, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, HIPEC, patient selection, serum tumour markers, peritoneal carcinomatosis, peritoneal metastases
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169548 (URN)10.1097/SLA.0b013e318254f281 (DOI)000312261000038 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    3. Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    Open this publication in new window or tab >>Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    2012 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

    Place, publisher, year, edition, pages
    Oxford University Press, 2012
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-165543 (URN)10.1093/annonc/mdr301 (DOI)000300733300016 ()21685413 (PubMedID)
    Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
    4. Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Open this publication in new window or tab >>Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Show others...
    2013 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed) Published
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-172441 (URN)10.1186/1471-2407-13-435 (DOI)000325079100001 ()
    Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2017-12-07Bibliographically approved
  • 40.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dranichnikov, Faoz
    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.
    Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy Treatment of Colorectal Peritoneal Metastases: Cohort Analysis of High Volume Disease and Cure Rate2014In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 110, no 2, p. 203-206Article in journal (Refereed)
    Abstract [en]

    Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) treatment of colorectal peritoneal metastases (PM) is an established treatment alternative. The study aim was, first, to investigate the outcome of high-volume disease defined by the peritoneal cancer index (PCI) 20; second, to report the long-term disease-free survival of patients with >5 years observation. Methods: Consecutive patients with colorectal PM from a prospective HIPEC database between 2004 and 2010 were included, 67 patients. Clinicopathological and outcome parameters were compared between low PCI (n = 40) and high PCI (n = 27). A subgroup analysis on patients with >5 years observation was performed (n = 32). Disease-free survival after 5 years defined cure. Results: Median overall survival (OS) was 28 months, low PCI-group 33 months versus high PCI-group 17 months (P = 0.03). Median OS of patients with complete CRS (n = 56) was 30 months, low PCI-group 37 months versus high PCI-group 27 months (P = 0.2), with 5-year survival of 31% and 21%, respectively. No difference in morbidity/mortality. The cure rate was 22% in the subgroup (7/32) and 28% in those with complete CRS (7/25). Two patients in the cured group had PCI 29 and 34. Discussion: Treatment of high-volume disease may result in long-term survival and even cure. The key is to reach a complete CRS. The overall cure rate is 22%. 

  • 41.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ehrsson, H
    Wallin, I
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis2013In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, no 3, p. 533-540Article in journal (Refereed)
    Abstract [en]

    Purpose

    Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin’s systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.

    Methods

    Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m2,doxorubicin 15 mg/m2) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).

    Results

    The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0–90 min of 2.87 mM·min and estimated 0–60 min of 2.45 mM·min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.

    Conclusions

    Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate

  • 42.
    Cashin, Peter H.
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2013In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 20, no 13, p. 4183-4189Article in journal (Refereed)
    Abstract [en]

    Background. There are three prognostic scores for the cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal) score, the peritoneal surface disease severity score (PSDS), and the prognostic score (PS). The aim was to determine which prognostic score had the best prognostic value. Methods. Between 2006 and 2010, a total of 77 patients with peritoneal metastases fromcolorectal cancer underwent CRS/HIPEC treatment. The COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having sufficient data. The end points were prediction of open-and-close cases (n = 9), R1 resections (n = 41), and survival of <12 months (n = 18). Area under the receiver operating characteristic curves (accuracy) was compared. Subgroup analysis was performed on patients not previously used for the development of the COREP score (n = 24). Multivariable logistic regressions of the three end points were performed as well as Cox regression for overall survival. Furthermore, COREP and peritoneal cancer index were compared. Results. For open-and-close case prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87 and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS. For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77 %, respectively. For prediction of survival of <12 months, accuracy was 83 and 84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only independent prognostic factor in all four multivariable analyses. A COREP score of >= 6 identified patients with poor survival more accurately than a PCI of >20. Conclusions. The COREP score predicted open-and-close cases, R1 resections, and poor survival better than PSDS and PS. COREP better identifies patients with poor survival than intraoperative PCI.

  • 43.
    Cashin, Peter H
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed)
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

  • 44.
    Cashin, Peter H
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

  • 45.
    Cashin, Peter H
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed)
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

  • 46.
    Cashin, Peter H.
    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.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Response to comments on 'Cytoreductive surgery and intraperitoneal chemotherapy'2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, p. 1012-1012Article in journal (Refereed)
  • 47.
    Cashin, Peter H
    et al.
    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.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlsson, Henning
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    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.
    Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed)
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

  • 48.
    Cashin, Peter H.
    et al.
    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. Uppsala Canc Clin, Uppsala, Sweden..
    Spang, N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Syk, I.
    Skane Univ Hosp, Dept Surg, S-21428 Malmo, Sweden..
    Frodin, J. E.
    Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Torkzad, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial2016In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 53, p. 155-162Article in journal (Refereed)
    Abstract [en]

    Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).

  • 49.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lundberg, Lars Göran
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ejerblad, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Acquired haemophilia A and Kaposi's sarcoma in an HIV-negative, HHV-8-positive patient: a discussion of mechanism and aetiology2010In: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 124, no 1, p. 40-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acquired haemophilia A (AHA) is a rare bleeding disorder caused by an imbalance in the immune system leading to the production of factor VIII antibodies. In half of the cases, the underlying cause is not known. CLINICAL HISTORY: We report on a patient with AHA and Kaposi's sarcoma (KS), which is caused by the human herpes virus 8 (HHV-8). The patient presented with appendicitis and developed several severe post-operative haemorrhages. He spent 3 months in intensive care due to long and difficult infections. While recuperating on the ward, the patient developed KS in the lower extremities. He had a positive HHV-8 infection. DISCUSSION/CONCLUSION: Due to its latency and replication in the lymphoid system, HHV-8 is an ideal candidate for causing an imbalance in the immune system in susceptible patients. Our conclusion is that AHA was caused or prompted by the HHV-8 infection. Since HHV-8 viral infection is often subclinical, viral testing might be an important tool in acquired haemophilia diagnostics even when viral symptoms are absent.

  • 50.
    Cashin, Peter
    et al.
    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 Radiology, Oncology and Radiation Science, Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andréasson, Håkan
    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.
    Appendiceal Adenocarcinoids with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy: a retrospective study of in vitro drug sensitivity and survival2011In: Clinical Colorectal Cancer, ISSN 1533-0028, Vol. 10, no 2, p. 108-112Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (MC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology.

    Methods: Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC.

    Results: Patients with completeness of cytoreduction score (CC) 1 (16.4 months). In the CC 1 group. For standard drugs, tumor cells from MC and CRC were equally sensitive; except for docetaxel, to which MC was more sensitive than CRC.

    Conclusion: The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of MC, although other drugs, eg, docetaxel, might be more active.

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