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  • 1. 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.

  • 2.
    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.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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)
  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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)
  • 12.
    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.

  • 13.
    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).

  • 14.
    Cashin, Peter
    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. Uppsala Canc Clin, Uppsala, Sweden.
    Syk, I.
    Lund Univ, Sect Surg, Dept Clin Sci, Malmo, Sweden.
    Frodin, J. E.
    Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 983-990Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

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

    Aim: 

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

    Method: 

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

    Results: 

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

    Conclusion: 

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

  • 16.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    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.
    Olsen, Leif
    Akad Sjukhuset, Dept Pediat Surg, S-75185 Uppsala, Sweden..
    Wester, Tomas
    Karolinska Univ Hosp, Dept Pediat Surg, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Posterior sagittal anorectoplasty results in better bowel function and quality of life in adulthood than pull-through procedures2015In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 50, no 9, p. 1556-1559Article in journal (Refereed)
    Abstract [en]

    Background/purpose: The short-term outcome of posterior sagittal anorectoplasty (PSARP) procedure has been reported to be better than after abdominoperineal or abdominosacroperineal (AP) procedures. This study aimed to investigate the long-term functional outcome and quality of life after PSARP in adulthood and compare with the outcome after AP procedures. Methods: Twenty-four patients operated with PSARP at the Department of Pediatric Surgery, Uppsala, Sweden, from 1984 to 1993 were identified. They were compared with 20 patients that underwent AP pull-through procedures from 1974 to 1983. The patients were sent validated bowel function and quality of life (SF-36) questionnaires. Sixteen PSARP (median age 21, five females) patients and fourteen AP patients (seven abdominosacroperineal and seven abdominoperineal pull-throughs, median age 32, seven females) responded and were included in the study. Results: The median Miller incontinence score was 1 (range 0-13) in the PSARP group and 10 (range 3-16) in the pull-through group (P = 0.0042). The use of underwear protection and oral loperamide was significantly less frequent in the PSARP group (P = 0.0096 and 0.0021 respectively). The SF-36 scores of Vitality, Mental health and Mental Cluster Scale were higher in the PSARP group (P = 0.0291, 0.0500, 0.0421 respectively). Conclusions: PSARP results in superior bowel function and better quality of life in adulthood compared with AP procedures for the repair of anorectal malformations.

  • 17.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Karlbom, Urban
    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.
    Wester, Tomas
    Department of Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Long-term outcome after free autogenous muscle transplantation for anal incontinence in children with anorectal malformations2010In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 45, no 10, p. 2036-2040Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Patients with high anorectal anomalies are often incontinent after reconstruction, particularly with the older forms of surgical treatment, that is, anorectal pull-through or Stephen's operations. In 1974, a new treatment for anal incontinence in children was introduced at the Akademiska Hospital: free autogenous muscle transplantation (FAMT) to the perirectal area. All the patients receiving FAMT were totally incontinent before the procedure and had no rectal sensitivity. The aim of this study was to evaluate the long-term functional outcome of this procedure. METHODS: Twenty-two patients (17 males) operated on with FAMT below the age of 15 years were identified through records. One of the patients had died, and 2 were not available for follow-up. The remaining 19 were sent a validated bowel function questionnaire, and 15 (78.9%) of 19 patients responded (12 males). These 15 patients were compared with 15 patients with the same sex, age, and a similar malformation from our patient database. RESULTS: At follow-up, after an average of 30 years postoperatively, 2 of 15 patients with FAMT had a stoma compared with 3 of 15 in the control group. The Miller incontinence score had a mean of 6.2 (median, 6; range, 0-15) in the FAMT group and 3.7 (median, 4; range, 0-12) in the control group. All patients in both groups could sense stool, and 11 of 13 patients in the FAMT group could distinguish between feces and flatus. CONCLUSIONS: The patients with FAMT had a slightly inferior anorectal function compared with the controls. Considering they were all totally incontinent before FAMT, we conclude that FAMT has an acceptable effect 30 years postoperatively. Therefore, we find that FAMT could be an alternative for anorectal malformation patients who are totally incontinent.

  • 18.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    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.
    Wester, Tomas
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?2017In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, no 3, p. 463-468Article in journal (Refereed)
    Abstract [en]

    Background/purpose

    Knowledge about the functional outcome in adults with anorectal malformations is essential to organize structured transition to adult care for this patient group. The aim of this study was to investigate the functional outcome and quality of life in adults with anorectal malformations characterized according to the Krickenbeck classification.

    Methods

    Of 256 patients diagnosed with anorectal malformations at our institution in 1961–1993, 203 patients could be traced and were invited to participate in the study. One hundred and thirty-six patients replied (67%) and were compared with one hundred and thirty-six population based sex and age-matched controls. Patients and controls were evaluated with both a validated questionnaire as well as a study-specific questionnaire to assess bowel function. SF-36 was used for quality of life. Outcome in nine incontinence-related parameters, 10 constipation-related, 6 urogenital function-related, and 13 quality of life parameters were assessed in the patients and compared to the outcome of controls as well as to the type of anorectal malformations according to the Krickenbeck classification.

    Results

    The ARM-patients had an inferior outcome (P < 0.05) for all incontinence parameters, 8 of 10 parameters for constipation, 2 of 6 for urogenital function and 7 of 13 quality of life parameters. Patients with rectobulbar and vestibular fistulas had the worst statistical outcome but patients with cloaca and rectoprostatic/bladder-neck fistula had worse outcome in absolute numbers. Forty-four patients (32%) reported incontinence of stool at least once a week and 16 (12%) had a permanent colostomy.

    Conclusions

    The functional outcome and quality of life in adults with anorectal malformations are closely related to the type of malformation. A large proportion of the patients have persistent fecal incontinence, constipation and sexual problems that have a negative influence on their quality of life. Structured multidisciplinary follow-up of adults with anorectal malformations by pediatric and colorectal surgeons, as well as urologists and gynecologists is therefore advocated.

  • 19.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Karlbom, Urban
    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.
    Wester, Tomas
    Karolinska Univ Hosp, Dept Pediat Surg, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Persistent fecal incontinence into adulthood after repair of anorectal malformations2019In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 34, no 3, p. 551-554Article in journal (Refereed)
    Abstract [en]

    Purpose: Persistent fecal incontinence beyond childhood is common in ARM patients. The aim of this study was to analyze a consecutive series of adult patients with persistent incontinence, establish the causes, and evaluate whether further treatment could be offered. Methods: Forty-four adult ARM patients with reported incontinence were invited. Eighteen patients (11 males, median age 40.5 years, range 18-50 years) accepted and underwent clinical examination, rectoscopy, and 3D-ultrasound. Five had previously been treated with secondary surgery to improve continence. Results: Seventeen of the 18 patients had abnormal findings at examination. Eight patients had obstruction of the reconstructed anus. Eleven patients had sacral deformities. Nine patients had a defect in the external anal sphincter and nine patients could not contract the sphincter on demand. Five patients had significant prolapse of mucosa. In one patient, the neoanus was totally misplaced, one patient had a rectovaginal fistula, and one patient had short bowel syndrome due to several small bowel resections. Ten patients were offered conservative and five surgical treatment. Conclusions: This case series of adults shows that a majority of the patients can be offered further treatment. This indicates a need for structured follow-up of ARM patients into adulthood.

  • 20.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sonesson, Ann-Cathrine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Wester, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence2009In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 6, p. 1101-1106Article in journal (Refereed)
    Abstract [en]

    PURPOSE: NASHA Dx gel has been used extensively for treatments in the field of urology. This study was performed to evaluate NASHA Dx gel as an injectable anal canal implant for the treatment of fecal incontinence. METHODS: Thirty-four patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were injected with 4 x 1 ml of NASHA Dx gel, just above the dentate line in the submucosal layer. The primary end point was change in the number of incontinence episodes and a treatment response was defined as a 50 percent reduction compared with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS: The median number of incontinence episodes during four weeks was 22 (range, 2 to 77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders at 6 months, compared with 19 (56 percent) at 12 months. No long-term side effects or serious adverse events were reported. CONCLUSIONS: Submucosal injection of NASHA Dx gel is an effective treatment for fecal incontinence. The effect is sustained for at least 12 months. The treatment is associated with low morbidity.

  • 21.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wester, T
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents2013In: Techniques in Coloproctology, ISSN 1123-6337, E-ISSN 1128-045X, Vol. 17, no 4, p. 389-395Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Stabilized non-animal hyaluronic acid/dextranomer (NASHA® Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.

    METHODS:

    Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.

    RESULTS:

    Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.

    CONCLUSIONS:

    Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.

  • 22.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wester, Tomas
    Astrid Lindgren Childrens Hosp, Dept Pediat Surg, Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Long-Term Outcome after Dynamic Graciloplasty for Treatment of Persistent Fecal Incontinence in Patients with Anorectal Malformations2019In: European journal of pediatric surgery, ISSN 0939-7248, E-ISSN 1439-359X, Vol. 29, no 3, p. 276-281Article in journal (Refereed)
    Abstract [en]

    Purpose Dynamic graciloplasty (DGP) has been used to treat severe fecal incontinence since the 1980s. Previous studies have shown an inferior outcome in patients with anorectal malformations (ARMs). Our experience has been that DGP has been appreciated by ARM -patients. The objective of the study was to evaluate the long-term outcome of DGP in our patients with ARM compared with patients with other underlying conditions. Materials and Methods Twenty-three patients operated with DGP at our institution from 1996 to 2010 were sent validated bowel function and quality of life questionnaires. Eighteen of 23 responded. Seven had ARM and 11 had other etiologies of fecal incontinence. The mean follow-up time was 11.6 years (range, 5-17). Results Four of 7 of the patients with ARM and 8 of 11 of patients with other etiologies used their implants at follow-up. The Miller incontinence score was slightly higher for patients with ARMs, but they had less constipation and higher Fecal Incontinence Quality of Life (FIQL)- and 36-Item Short Form Health Survey (SF-36) scores. None of the differences were statistically significant. Conclusion This study cannot confirm earlier reports in which DGP has an inferior outcome in patients with ARM. We therefore believe that the procedure should remain a treatment option for selected patients.

  • 23.
    Elias, Khalid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bekhali, Zakaria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Changes in bowel habits and patient-scored symptoms after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch2018In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 14, no 2, p. 144-149Article in journal (Refereed)
    Abstract [en]

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

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

    Setting: University hospital in Sweden.

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

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

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

  • 24.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ekbom, Anders
    Department of Medicine, Clinical Epidemiology Unit, Karolinska institutet.
    Sandin, Fredrik
    Regional Cancer Centre, Uppsala University Hospital.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Increased incidence of bowel cancer after non-surgical treatment of appendicitis2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 11, p. 2067-2075Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis.

    PATIENTS AND METHODS: Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated.

    RESULTS: Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1).

    CONCLUSION: Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis.

  • 25.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ghanipour, Lana
    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.
    Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2016In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 23, no 4, p. 1149-1156Article in journal (Refereed)
    Abstract [en]

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  • 26.
    Enblad, Malin
    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.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Risk factors for appendiceal and colorectal peritoneal metastases2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 997-1005Article in journal (Refereed)
    Abstract [en]

    Background

    Early diagnosis to target minimal volume disease has received increased attention in the management of appendiceal and colorectal peritoneal metastases (PM). This study aimed to identify risk factors for appendiceal, colon and rectal PM.

    Methods

    Data were retrieved from the Swedish Colorectal Cancer Registry for all patients undergoing bowel resection of appendiceal and colorectal tumours, in Sweden, 2007–2015. Risk factors for synchronous and metachronous PM were analysed with multivariate logistic and Cox proportional hazard regression models.

    Results

    Synchronous PM was most common in appendiceal cancer (23.5%), followed by colon (3.1%) and rectal (0.6%) cancer. The 5-year cumulative incidence was 9.0% for appendiceal, 2.5% for right colon, 1.8% for left colon and 1.2% for rectal cancer. In appendiceal cancer (n = 327), T4, N2, mucinous tumour, and non-radical surgery were associated with PM. In colon cancer (n = 24,399), synchronous PM were primarily associated with T4 (OR 18.37, 95% CI 8.12–41.53), T3 and N2 but also with N1, right-sided tumour, mucinous tumour, vascular and perineural invasion, female gender, age <60 and emergency surgery. These factors were also associated with metachronous PM. In rectal cancer (n = 10,394), T4 (OR 19.12, 95% CI 5.52–66.24), proximal tumour and mucinous tumour were associated with synchronous PM and T4 and mucinous tumour with metachronous PM.

    Conclusions

    This study shows that appendiceal cancer, right-sided colon cancer, advanced tumour and node stages and mucinous histopathology are the main high-risk features for PM and should increase the awareness of current or future PM.

  • 27.
    Enblad, Malin
    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.
    Terman, Alexei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pucholt, Pascal
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Viklund, Björn
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Prognostic importance of genetic alterations in colorectal peritoneal metastasesManuscript (preprint) (Other academic)
  • 28.
    Franck-Larsson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edebol Eeg-Olofsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Axelson, Hans W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 9, p. 1073-1083Article in journal (Refereed)
    Abstract [en]

    Objective

    Fecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms.

    Materials and methods

    Twenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound.

    Results

    Eleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05).

    Conclusion

    Lower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.

  • 29.
    Franck-Larsson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edebol-Eeg Olofsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Physiological and structural abnormalities in patients with systemic sclerosis and faecal incontinenceManuscript (preprint) (Other academic)
  • 30.
    Franck-Larsson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lower gastrointestinal symptoms and quality of life in patients with systemic sclerosis: a population-based study2009In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 21, no 2, p. 176-182Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the frequency and nature of bowel symptoms in a population-based cohort of patients with systemic sclerosis (SSc), compared with healthy controls, and to relate these symptoms to health-related quality of life (HR-QOL). METHOD: Seventy-nine SSc patients and 158 matched controls answered a validated questionnaire on gastrointestinal (GI) symptoms and Medical Outcomes Study Short Form Health Survey (SF-36). Modified Miller Score, a composite score measuring faecal incontinence, was computed. RESULTS: Abnormal stool consistency, bloating, a feeling of incomplete evacuation, faecal incontinence and rectal bleeding were more frequently reported by SSc patients than controls. The ability for anorectal discrimination, and deferring defecation was diminished in SSc patients. Bowel function affected general well being in 30% of patients and social life in 20%. Patients had lower SF-36 scores, that is, worse HR-QOL than controls. Modified Miller Score did not correlate to the SF-36 scores in patients, but other lower GI symptoms, especially abdominal pain and bloating, were associated with diminished HR-QOL. CONCLUSION: Lower GI symptoms, including faecal incontinence, are more common in patients with SSc than in healthy controls and are of consequence to the individual patient's life. The lower prevalence of anorectal discrimination in the SSc patients suggests a neuronal defect in these patients. Increased awareness of these symptoms might stimulate a search for new diagnostic and therapeutic strategies.

  • 31.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Anorektala sjukdomar2009In: Läkemedelsboken, Stockholm: Apoteket AB , 2009, p. 142-149Chapter in book (Other academic)
  • 32.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Andersson, Magnus
    Åkerlund, Jan-Erik
    Börjesson, Lars
    Long-term outcome after surgery for Crohn's anal fistula2016In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 18, p. 80-85Article in journal (Refereed)
    Abstract [en]

    AIM: Treatment of Crohn's anal fistula remains challenging and little is known about factors associated with healing. The aim of this study was to assess the rate of healing after surgical treatment and analyse clinical variables related to healing.

    METHOD: 119 patients (63 female, mean age 36 (±13.7) years with histopathologically verified Crohn's disease underwent a surgical procedure for anal fistula at four main referral centres in Sweden, January 1998 - December 2009. Baseline and treatment-related variables were recorded and analysed for correlation with fistula healing at a final follow-up at a mean 7.2 (median 7.1, 1.0-17.5) years.

    RESULTS: Of the 119 patients 62 (52%) were healed at final follow-up. Fourteen healed after one procedure and the remaining 48 healed after a further median of 4.0 (2-20) procedures. Ten (8%) patients were subjected to a proctectomy. Final healing was more common in patients operated with a procedure aiming at eradicating the fistula (P=0.0001), without proctitis (P=0.02), and a shorter duration of Crohn' disease (P=.0019).

    CONCLUSION: Long-term healing of a Crohn's anal fistula can be expected in about half of the patients, usually after repeated surgical treatment. The probability for cure was higher when a curative operation was performed in a patient without proctitis and a shorter duration of Crohn's disease. An attempt to close a Crohn's anal fistula is thus often worthwhile. This article is protected by copyright. All rights reserved.

  • 33.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sakral nervstimulering ger bra effekt vid anal inkontinens: Indikationsområdena för detta minimalinvasiva ingrepp vidgas alltmer2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 10, p. 682-684Article in journal (Refereed)
  • 34.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mellgren, Anders
    Matzel, Klaus E.
    Hull, Tracy
    Johansson, Claes
    Bernstein, Mitch
    Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial2011In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 377, no 9770, p. 997-1003Article in journal (Refereed)
    Abstract [en]

    Background: Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence. Methods In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826. Findings 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2.36, 95% CI 1.24-4.47, p=0.0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess). Interpretation Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment.

  • 35.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sonesson, A-C
    Lindberg, B
    Åkerud, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Results after sacral nerve stimulation for chronic constipation2015In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 5, p. 734-739Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sacral nerve stimulation is an established treatment for fecal incontinence and initial reports describe successful results also in subjects with chronic constipation.

    METHODS: Consecutive patients with slow transit or outlet obstruction type constipation were offered external stimulation through a test electrode inserted in a sacral foramen during a 3-week period. The symptomatic evaluation was based on the number of bowel movements and a validated obstructed defecation score (ODS). A permanent implant was performed provided an overall 50% decrease in symptoms was observed.

    KEY RESULTS: In total, 44 patients with chronic constipation were treated with a 3-week test stimulation. Fifteen experienced a 50% reduction of symptoms and received a permanent implant. Four of the 15 with permanent implants were explanted during the course of the study. Five subjects (11% of original group) reported sustained symptom relief at final follow-up after a mean of 24 months (range 4-81). Mean ODS score did not change during the treatment. Patients with predominantly slow transit constipation or outlet obstruction did not differ concerning success rate.

    CONCLUSIONS & INFERENCES: Sacral nerve stimulation has limited efficacy in unselected patients with chronic constipation and cannot be recommended for treatment on routine basis.

  • 36.
    Gustafsson, Ulla Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Randomized clinical trial of local gentamicin-collagen treatment in advancement flap repair for anal fistula2006In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 93, no 10, p. 1202-1207Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 37.
    Gustafsson, Ulla-Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Liss, Anders
    Graf, Wilhelm
    Intraoperative changes in mucosal blood flow in advancement flap repair of anal fistula.Manuscript (Other academic)
  • 38.
    Gustafsson, Ulla-Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    Graf, Wilhelm
    Factors associated with the risk of idiopathic anal fistula disease:: a case-control studyManuscript (Other academic)
  • 39.
    Hansson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Quality of life in peritoneal carcinomatosis after cytoreductive surgery and intraperitoneal chemotherapy2012Article in journal (Refereed)
    Abstract [en]

    Background:

    Cytoreductive surgery (CRS) plus intraperitoneal chemotherapy (IPC) is considered the most optimal treatment for peritoneal carcinomatosis (PC). Health-related quality of life (HRQL) after treatment is largely unknown. The aims were to assess HRQL in patients with PC treated with CRS and IPC and to analyse the influence of clinical variables on HRQL.

    Methods:

    HRQL was assessed prospectively between November 2001 and March 2005 in 64 consecutive patients with PC through two different self-administered instruments, EORTC QLQ-C30 v3.0 (QLQ-C30) and the SF-36 Health Survey (SF-36), preoperatively, and after 3 and 8 months.

    Results:

    For QLQ-C30, 44 (69%) and for SF-36, 42 (66%) out of 64 patients had a complete follow-up. Most scales were worsened at baseline compared to reference in both instruments. HRQL was reduced at 3-months in QLQ-C30 (physical, role and emotional functioning) and in SF-36 (physical summary score). At 8-months, all scales returned to baseline in QLQ-C30, except physical functioning which was still reduced and dyspnoea that was worsened. In SF-36, all values returned to baseline levels. At 8-months, presence of a stoma worsened social functioning and a high peritoneal cancer index decreased social functioning and global QoL, the use of hyperthermic intraperitoneal chemotherapy and 30-days postoperative morbidity had no impact on HRQL.

    Conclusion:

    CRS with IPC results in reasonable short-term HRQL despite high initial morbidity and an initial decrease in HRQL parameters. The study adds to the notion that this treatment appears beneficial in light of probable life prolongation, despite considerable toxicity.

  • 40.
    Hansson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Postoperative adverse events and long-term survival after cytoreductive surgery and intraperitoneal chemotherapy2009In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 35, no 2, p. 202-208Article in journal (Refereed)
    Abstract [en]

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

  • 41.
    Hansson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics.
    Garske, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Single-photon emission computed tomography for prediction of treatment results in sequential intraperitoneal chemotherapy at peritoneal carcinomatosis2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140Article in journal (Refereed)
    Abstract [en]

    Background:

    Cytoreductive surgery and intraperitoneal chemotherapy (IPC) treatment can improve survival in peritoneal carcinomatosis. One of the reasons for failure of sequential postoperative intraperitoneal chemotherapy (SPIC) is lack of distribution of the chemotherapy in the peritoneal cavity. The primary aim of this study was to evaluate single-photon emission computed tomography (SPECT) as a predictor of successful SPIC treatment and prognosis. A secondary aim was to assess the relationship between SPECT, feasibility of SPIC, and clinical variables.

    Methods:

    Fifty-one patients (mean age 52 years, range 14-74, 20 women) were treated with Cytoreductive surgery and SPIC. SPECT studies with intraperitoneal (i.p.) Technetium-99 via a Port-a-Cath (PaC) were performed before the second course of treatment. The i.p. distribution was registered as a detected volume (DV) at four different threshold settings (1, 2, 5, and 10%) of the global maximum intensity of the SPECT examination. A calculation model for SPECT and clinical variables was tested.

    Results:

    The DV measured in the SPECT examination predicted the number of subsequent SPIC courses. The highest correlation (R=0.45) for DV was in the 2% threshold setting. Patients with a DV2% lower than mean reached two SPIC courses and patients with a DV2% higher than mean reached six SPIC course. Height correlated to higher DV and a higher number of SPIC courses. Patients with a height lower than mean reached a DV2% at 3930 ml and patients higher than mean reached a DV2% at 5507 ml. A taller person could tolerate more SPIC courses (R=0.28) and patients with a height higher than mean reached six SPIC courses; patients with a height lower than mean reached four courses. There was no correlation between DV and survival.

    Conclusion:

    The feasibility of performing SPIC without further surgical intervention can be predicted by SPECT, and it might therefore be an instrument to select which patients should preferably be treated with alternative therapy.

  • 42.
    Hassan, Saadia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Laryea, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Felth, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Fayad, Walid
    Linder, Stig
    Rickardson, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pålman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Novel activity of acriflavine against colorectal cancer tumor cells2011In: Cancer Science, ISSN 1347-9032, E-ISSN 1349-7006, Vol. 102, no 12, p. 2206-2213Article in journal (Refereed)
    Abstract [en]

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

  • 43. Johannsson, Helgi O
    et al.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Authors' reply: Randomized clinical trial of the effects on anal function of Milligan-Morgan versus Ferguson haemorrhoidectomy (Br J Surg 2006; 93: 1208-1214)2007In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 94, no 1, p. 122-122Article in journal (Refereed)
  • 44.
    Johannsson, Helgi Orn
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Interfaculty Units, Centrum för klinisk forskning Dalarna.
    Graf, Wilhelm
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Bowel habits in hemorrhoid patients and normal subjects.2005In: Am J Gastroenterol, ISSN 0002-9270, Vol. 100, no 2, p. 401-6Article in journal (Refereed)
  • 45. Johannsson, Helgi Orn
    et al.
    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.
    Functional and Structural Abnormalities After Milligan Hemorrhoidectomy: A Comparison With Healthy Subjects2013In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 56, no 7, p. 903-908Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fecal incontinence is a rare but well-known adverse effect of hemorrhoidectomy. OBJECTIVE: The objective of this study was to identify possible reasons for incontinence after hemorrhoidectomy. DESIGN: We conducted a retrospective comparative study. SETTINGS: The study was performed in 1 university hospital and 1 general district hospital serving 2 counties in central Sweden. PATIENTS: In a cohort of 418 patients with consecutive Milligan hemorrhoidectomies, 40 reported fecal incontinence that was attributed to surgery. Of these, 19 patients agreed to participate. Fifteen age- and sex-matched patients from the same cohort who were operated on, but without symptoms of incontinence, were also studied, as was a third reference group of 19 age- and sex-matched persons serving as a population-based control group. INTERVENTION: All of the participants answered a bowel function questionnaire and underwent clinical evaluation, including rectoscopy, anal manometry, saline infusion test, and endoanal ultrasound. MAIN OUTCOME MEASURES: We evaluated anal resting and squeeze pressures, sphincter defects, and continence function. RESULTS: The symptomatic patients had higher incontinence scores than the control groups (p = 0.00002). The mean resting pressure at the high-pressure zone was also reduced in this group (p = 0.047). External sphincter injuries were detected in 4 (20%) of 19 subjects compared with none in the control group (p = 0.11). Saline infusion test in the patients reporting incontinence showed reduced ability to hold liquids compared with healthy controls (p = 0.004). LIMITATIONS: This study was limited by selection bias and limited numbers in the groups. CONCLUSIONS: In the group of patients reporting incontinence after hemorrhoidectomy, there was a proportion with sphincter defects and impaired sphincter function. These results indicate a need for cautious patient selection and improved or alternative surgical techniques.

  • 46.
    Johannsson, Helgi Örn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Graf, Wilhelm
    Påhlman, Lars
    Randomized Clinical Trial of Milligan-Morgan versus Ferguson HaemorrhoidectomyArticle in journal (Refereed)
  • 47.
    Johannsson, Helgi Örn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Randomized clinical trial of the effects on anal function of Milligan-Morgan versus Ferguson haemorrhoidectomy2006In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 93, no 10, p. 1208-1214Article in journal (Refereed)
    Abstract [en]

    Background: Studies of haemorrhoidectomy usually report postoperative pain, healing and complications, but rarely consider anal function in the longer term. The primary aim of this randomized trial was to compare long-term changes in anal function after open (Milligan-Morgan) and closed (Ferguson) haemorrhoidectomy.

    Methods: A total of 225 patients were included in the trial, 115 in the open group and 110 in the closed group. Continence changes were recorded by means of validated questions and an incontinence score. Pain was self-reported using a visual analogue scale.

    Results: Postoperative pain and complications did not differ between the groups. Time to recovery was 17 days in the Milligan-Morgan group and 15 days in the Ferguson group. After 1 month the wounds were healed in 57.0 per cent of patients in the open group and 70.6 per cent of those in the closed group (P = 0.058). At 1 year, 78.9 per cent of the Milligan-Morgan group and 85.3 per cent of the Ferguson group reported no continence disturbance (P = 0.072). The incontinence score was improved at 1 year in the closed group (P = 0.015), but was unchanged in the open group (P = 0.645). Patients who had the Ferguson procedure were more satisfied with the outcome of surgery (P = 0.047).

    Conclusion: Closed Ferguson haemorrhoidectomy was superior to the open Milligan-Morgan procedure with respect to long-term anal continence and patient satisfaction.

  • 48.
    Jóhannsson, Helgi Örn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Graf, Wilhelm
    Påhlman, Lars
    Structural Abnormalities and Disturbes Anorectal Function after Milligan-Morgan Haemorrhoidectomy. A Comparison with Healthy Control SubjectsManuscript (Other academic)
  • 49.
    Karlbom, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Lundin, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Graf, W
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Anorectal physiology in relation to clinical subgroups of patients with severe constipation.2004In: Colorectal Dis, ISSN 1462-8910, Vol. 6, no 5, p. 343-9Article in journal (Refereed)
  • 50.
    Karlbom, Urban
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Eeg-Olofsson, Karin Edebol
    Department of Neuroscience.
    Graf, Wilhelm
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Evaluation of the paradoxical sphincter contraction by a strain/squeeze index in constipated patients.2005In: Dis Colon Rectum, ISSN 0012-3706, Vol. 48, no 10, p. 1923-9Article in journal (Refereed)
12 1 - 50 of 73
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