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1.
  • Andersson, Magnus V., et al. (author)
  • Kirurgi – omistligt komplement till medicinsk behandling
  • 2009
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:45, s. 3003-9
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Andréasson, Håkan, et al. (author)
  • Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
  • 2013
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 40:8, s. 930-936
  • Journal article (peer-reviewed)abstract
    • 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.
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4.
  • Andreasson, Håkan, et al. (author)
  • Histopathological classification of pseudomyxoma peritonei and the prognostic importance of PINCH protein
  • 2012
  • In: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Andréasson, Håkan, et al. (author)
  • Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
  • 2012
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 38:10, s. 962-968
  • Journal article (peer-reviewed)abstract
    • 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.
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6.
  • Birgisson, Helgi, et al. (author)
  • Patients with colorectal peritoneal metastases and high peritoneal cancer index may benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
  • 2020
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 46:12, s. 2283-2291
  • Journal article (peer-reviewed)abstract
    • Background: Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI <= 20 treated with CRS and HIPEC to those having open-close/debulking procedure only.Methods: All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI <= 20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking.Results: Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI <= 20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI <= 20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years.Conclusion: Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken.
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7.
  • Bjersand, Kathrine, et al. (author)
  • Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei
  • 2015
  • In: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 22, s. S810-S816
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter H, 1984-, et al. (author)
  • Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
  • 2013
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 435-
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter H., et al. (author)
  • Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
  • 2013
  • In: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 20:13, s. 4183-4189
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter H, 1984-, et al. (author)
  • Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis : Prognosis and Treatment of Recurrences in a Cohort Study
  • 2012
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 38:6, s. 509-515
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter H, 1984- (author)
  • Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer : Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity
  • 2012
  • Doctoral thesis (other academic/artistic)abstract
    • Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperthermic intraperitoneal chemotherapy-HIPEC vs. sequential postoperative intraperitoneal chemotherapy-SPIC) and choice of drugs for IPC were the aspects covered in this thesis.The treatment outcome of CRS and IPC according to the median overall survival ranged from 24 to 34 months with 5-year overall survival ranging from 20 to 40% depending on the IPC treatment administered. Furthermore, the 5-year disease-free survival was impressive at 32% for patients receiving HIPEC. This establishes the curative potential of this treatment. Due to current inadequacies of radiological imaging, a score (Corep score) was developed for patient selection purposes. This score had a sensitivity of 80% and specificity of 100% in identifying patients with short cancer-specific survival after the treatment (<12 months). Further studies are needed to elucidate the clinical usefulness of the Corep score. HIPEC was associated with better survival than the SPIC method at similar morbidity and mortality rates, suggesting that HIPEC be the method of preference. Concerning the choice of drugs, the last study investigated the chemo-sensitivity of different PM tumour-types with a special focus on CRC. While CRC samples were generally more resistant, the ratio of the in vivo concentration compared to the ex vivo concentration giving a 50% tumour cell death showed that oxaliplatin had the best profile across all PM tumour types as well as for CRC. This needs further confirmation in a clinical trial.
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  • Cashin, Peter H., et al. (author)
  • Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases : A randomised trial
  • 2016
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 53, s. 155-162
  • Journal article (peer-reviewed)abstract
    • 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).
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  • Cashin, Peter H, et al. (author)
  • Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis : a case-control study
  • 2012
  • In: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 23:3, s. 647-652
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter H, 1984-, et al. (author)
  • Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
  • 2012
  • In: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 256:6, s. 1078-1083
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Cashin, Peter Harald, 1984-, et al. (author)
  • Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent colorectal peritoneal metastases
  • 2024
  • In: Surgery Open Science. - : Elsevier. - 2589-8450. ; 20, s. 45-50
  • Journal article (peer-reviewed)abstract
    • Background:Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated.Objectives:To evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease.Methods:Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated.Results:Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30-58) in the interventional group and 19 months (95%CI: 15-24) in the palliative group (HR 0.35 95%CI: 0.20-0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38-45).Conclusion:After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.
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  • Cashin, Peter, 1984-, et al. (author)
  • Peritoneal mesothelioma in Sweden : A population-based study
  • 2019
  • In: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:14, s. 6468-6475
  • Journal article (peer-reviewed)abstract
    • The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P =.04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P =.03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.
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  • Cashin, Peter, 1984-, et al. (author)
  • Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases
  • 2018
  • In: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 44:7, s. 983-990
  • Journal article (peer-reviewed)abstract
    • 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.
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20.
  • Cashin, Peter, 1984-, et al. (author)
  • Sequential postoperative intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases : a narrative review
  • 2021
  • In: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 12, s. S131-S135
  • Research review (peer-reviewed)abstract
    • Sequential postoperative intraperitoneal chemotherapy (SPIC) is a chemotherapy abdominal infusion given as a postoperative adjuvant treatment for 6 months after cytoreductive surgery (CRS) for peritoneal surface malignancies. It has most commonly been used in conjunction with ovarian cancer where the SPIC treatment has been integrated with adjuvant systemic chemotherapy. This review investigates the role of SPIC in the setting of colorectal cancer with peritoneal metastases. The focus is on the CRS+SPIC combination treatment with no systemic chemotherapy component. Several cohort studies, several comparative studies, and one randomized trial have been reported with several important endpoints. The following aspects will be covered in this review: overall survival, disease-free survival, morbidity, quality-of-life, and cost-effectiveness. In comparison to systemic chemotherapy alone for isolated resectable colorectal peritoneal metastases, CRS+SPIC is superior concerning overall survival, has no difference in morbidity, is similar in quality-of-life, and SPIC is cast-effective. In comparison to HIPEC, results are conflicting in multivariate analysis; but in a univariate analysis HIPEC (most often combined with systemic adjuvant therapy) appears superior to SPIC alone (no systemic component). The future of SPIC is uncertain. However, a combination of HIPEC and SPIC +/- a systemic chemotherapy component is a possible direction to explore further.
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21.
  • Collin, Åsa (author)
  • Colorectal cancer : Aspects of staging, treatment, recurrence and survival
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Colorectal cancer is the third most common malignancy in the world, and major breakthroughs have been made regarding both surgical and oncological treatment. Still, postoperative complications, such as perineal infections after abdominoperineal resection (APR), are a major cause of morbidity, and distant recurrence rate is nearly 20%. In this thesis, means to improve postoperative infection rates, nodal staging in rectal cancer (and resulting overtreatment through (chemo)radiotherapy), cancer recurrence rates and survival, were investigated. In Paper I, the effects on complication rates, recurrence rates and survival of antibiotics applied locally after an APR, by means of a gentamicin-collagen sponge in the perineal wound, were analysed in a randomized setting. No difference was seen regarding any of the endpoints. The results suggest that local antibiotics can safely be omitted in APRs. Paper II investigated the effects of mechanical bowel preparation (MBP) on cancer recurrence and survival, among colon cancer patients undergoing a colon resection. Data from the Swedish randomized MBP trial were used. After follow-up, no improvement in recurrence rates or overall survival was seen, but cancer-specific survival was improved in the MBP group. In conclusion, MBP might be a prognostic favourable factor for outcome in colon cancer patients. In Paper III, the effect of new national guideline criteria for MRI nodal staging in rectal cancer was assessed, regarding the proportion of clinically positive nodes and staging accuracy, and resulting effects on preoperative (chemo)radiotherapy use. Comparing the two years prior to guideline implementation with the two years after implementation revealed a significant decrease in the proportion clinically positive nodes, but staging accuracy remained low, and (chemo)radiotherapy rates decreased with seemingly no correlation to guidelines. Thus, new guidelines decreased the rate of clinically positive nodes, but nodal accuracy remained poor and nodal staging should perhaps not be a criterion in preoperative treatment decisions. Paper IV investigated the impact of the total mesorectal excision quality, by means of the three Quirke grades, mesorectal (best quality), intramesorectal and muscularis propria (worst quality), on recurrence and survival, and assessed risk factors for intramesorectal or muscularis propria resection. Muscularis propria grade was associated with a higher local recurrence rate, but not with distant recurrence or survival. Several factors were associated with intramesorectal and muscularis propria grade, and more caution is warranted in these patients. In conclusion, this thesis provides insight into treatment choice, and the association of day-to-day treatment details with postoperative complications, recurrence and survival rates, as well as the challenges of nodal staging.
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22.
  • Collin, Åsa, et al. (author)
  • The effect of local gentamicin-collagen on perineal wound complications and cancer recurrence after abdominoperineal resection : a multicentre randomised controlled trial
  • 2013
  • In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 15:3, s. 341-346
  • Journal article (peer-reviewed)abstract
    • 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.
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23.
  • Danielson, Johan, 1975- (author)
  • Anorectal Malformations : Long-term outcome and aspects of secondary treatment
  • 2015
  • Doctoral thesis (other academic/artistic)abstract
    • Faecal incontinence (FI) is defined as the inability to control bowel movements. The causes of FI are many and diverse. One of the more uncommon reasons for FI is Anorectal Malformations (ARMs). An ARM is a congenital anomaly that affects somewhere between 1/2500 and 1/5000 live born babies. Many ARM patients have persistent FI. Several different procedures have been utilised to address this issue. This thesis aims to evaluate (1) the long-term outcome in adulthood of ARMs in relation to the modern Krickenbeck classification, and (2) scope for treating FI with transanal injection with dextranomer in non-animal stabilised hyaluronic acid (NASHA/Dx), in patients both with and without ARMs.All patients treated for ARMs in Uppsala up to 1993 were invited to participate in a questionnaire study of quality of life and function. The study included 136 patients and compared them with 136 age- and sex-matched controls. The Krickenbeck classification was found to predict functional outcome, and ARM patients had more problems with incontinence and obstipation, as well as inferior Quality of Life (QoL), compared with controls. Thirty-six patients with FI, owing to causes other than ARMs, were treated with transanal submucous injection of NASHA/Dx. The patients were monitored for two years after treatment. Significant reductions in both their incontinence score and the number of their incontinence episodes were achieved.  A significant improvement in QoL was observed in patients who had at least a 75% reduction in incontinence episodes. No serious complications occurred.A prospective study of transanal injection of NASHA/Dx was conducted on seven patients with persistent FI after ARMs. After six months a significant reduction in the number of incontinence episodes was obtained. A significant improvement in QoL was also found. No serious complications occurred.In conclusion, adult patients with ARMs have inferior outcome of anorectal function and QoL compared with controls. NASHA/Dx is effective and appears to be safe in treating FI in general. This effect seems to be the same in selected patients with persistent FI after ARMs.
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24.
  • Danielson, Johan, 1975-, et al. (author)
  • Change in Deferring Time Correlate to Improved Female Sexual Function after Anal Sphincter Repair: A Prospective Study
  • 2020
  • In: Open Journal of Obstetrics and Gynecology. - : Scientific Research Publishing, Inc.. - 2160-8792 .- 2160-8806. ; 10:05, s. 729-737
  • Journal article (peer-reviewed)abstract
    • Background: Many women suffer from sexual problems after anal sphincter tears due to obstetric trauma. Aim: The study aimed to assess changes in sexual function after anal sphincter repair. Methods: The study was a non-randomized prospective observational cohort study. Inclusion of the study was done at the University Hospital, Uppsala, Sweden, between 2002 and 2007. Thirty-nine consecutive female patients admitted for anal sphincter repair were invited to the study. Twenty patients accepted and were included, four were lost to follow up and one was unevaluable (due to the formation of a stoma) leaving a study group of 15 patients. The patients were assessed with questionnaires before surgery and at three and 12 months after surgery. Outcomes: Change in reported sexual activity and dyspareunia. Results: Before surgery, 12/15 patients reported that their sexual life was impaired due to anal incontinence. The corresponding figure at 12 months was 9/15 (p = 0.43). Three patients remained sexually inactive throughout the study, five patients increased their sexual activity and one had decreased activity. Out of the 12 who were active, four stated dyspareunia at baseline, and only one reported dyspareunia at 12 months. The mean Miller incontinence scores at baseline and 12 months were 10.1 and 8.7, respectively. The change in incontinence score did not differ between those with decreased, stable or increased sexual activity. However, there was a definite correlation (r = 0.54 - 0.60, p < 0.05) between change in sexual function and deferring time for stool. Clinical Implications: Operative management of anal sphincter tears alone is not curative for sexual problems due to anal incontinence but can be a part of the treatment. Strengths and Limitations: The study is a prospective study of sexual function. The limitations are that the questionnaires were not validated due to lack of such questionnaires at the time of the study and that the study population is quite small. Conclusion: Patients with a sphincter injury and fecal incontinence often have an impaired sexual function. Increased deferring time for stools after surgery increases the likelihood of improved sexual function.
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25.
  • Danielson, Johan, 1975-, et al. (author)
  • Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
  • 2013
  • In: Techniques in Coloproctology. - : Springer Science and Business Media LLC. - 1123-6337 .- 1128-045X. ; 17:4, s. 389-395
  • Journal article (peer-reviewed)abstract
    • 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 %.
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26.
  • Danielson, Johan, 1975-, et al. (author)
  • Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.
  • Other publication (other academic/artistic)abstract
    • Background/PurposeDuring the last decades injectable bulking therapy has emerged as a promising treatment option for fecal incontinence (FI). Very little has been published on the use of injectable bulking therapy on patients with persistent FI after anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.MethodsSeven adult patients with persistent FI after ARM were treated with perianal submucuos injection of NASHA/Dx. They were evaluated preoperatively and at three and six months after treatment with a validated bowel function questionnaire and a two-week bowel diary as well as FIQL and SF-36 quality of life questionnaires.ResultsBefore treatment mean Miller incontinence score was 13,7 and the mean number of incontinence episodes over two weeks was 20,7. At 6 months after treatment the corresponding figures were 10,7 (P=0,1088) and 5,3 (P=0,0180) respectively. No significant changes could be found in either FIQL or SF-36 scores. No serious adverse events occurred during the study.ConclusionsNASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Long-term follow up of larger patient series as well as studies on patients in adolescence are needed. 
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27.
  • Danielson, Johan, 1975-, et al. (author)
  • Injectable bulking treatment of persistent fecal incontinence in adult patients after anorectal malformations
  • 2020
  • In: Journal of Pediatric Surgery. - : W B SAUNDERS CO-ELSEVIER INC. - 0022-3468 .- 1531-5037. ; 55:3, s. 397-402
  • Journal article (peer-reviewed)abstract
    • Background/Purpose: Injectable bulking therapy has emerged as a treatment for fecal incontinence (IT, however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic add with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.Methods: Seven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FTQL and SF-36 quality of life questionnaires.Results: Before treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8-52). At 6 months, the corresponding figures were 53 (median 4, range 0-19, p = 0.018), and at 18 months the figures were 4.3 (median 2, range 1-20,p = 0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6 months was noted (p = 0.04). No serious adverse events occurred.Conclusions: NASHA/Dx is a promising treatment option for selected adult patients with persistent Ft after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed. 
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28.
  • Danielson, Johan, 1975-, et al. (author)
  • Long-Term Outcome after Dynamic Graciloplasty for Treatment of Persistent Fecal Incontinence in Patients with Anorectal Malformations
  • 2019
  • In: European journal of pediatric surgery. - : GEORG THIEME VERLAG KG. - 0939-7248 .- 1439-359X. ; 29:3, s. 276-281
  • Journal article (peer-reviewed)abstract
    • 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.
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29.
  • Danielson, Johan, et al. (author)
  • Long-term outcome after free autogenous muscle transplantation for anal incontinence in children with anorectal malformations
  • 2010
  • In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 45:10, s. 2036-2040
  • Journal article (peer-reviewed)abstract
    • 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.
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30.
  • Danielson, Johan, 1975-, et al. (author)
  • Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?
  • 2017
  • In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 52:3, s. 463-468
  • Journal article (peer-reviewed)abstract
    • Background/purposeKnowledge 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.MethodsOf 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.ResultsThe 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.ConclusionsThe 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.
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31.
  • Danielson, Johan, 1975-, et al. (author)
  • Persistent fecal incontinence into adulthood after repair of anorectal malformations
  • 2019
  • In: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 34:3, s. 551-554
  • Journal article (peer-reviewed)abstract
    • 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.
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32.
  • Danielson, Johan, et al. (author)
  • Posterior sagittal anorectoplasty results in better bowel function and quality of life in adulthood than pull-through procedures
  • 2015
  • In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 50:9, s. 1556-1559
  • Journal article (peer-reviewed)abstract
    • 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.
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33.
  • Danielson, Johan, et al. (author)
  • Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer : a new treatment option for fecal incontinence
  • 2009
  • In: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 52:6, s. 1101-1106
  • Journal article (peer-reviewed)abstract
    • 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.
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34.
  • Dranichnikov, Paul, MD, PhD Candidate, 1980-, et al. (author)
  • Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
  • 2021
  • In: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 28:12, s. 7772-7782
  • Journal article (peer-reviewed)abstract
    • Background Coagulopathy after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recognized but few details have been studied.Objectives The aim of this study was to investigate changes in coagulation biomarkers and their predictive ability for venous thromboembolism (VTE).Methods Patients undergoing CRS and HIPEC at Uppsala University Hospital, Sweden, from 2004 to 2014 were included in a prospective study of coagulation biomarkers. Prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, D-dimer, and platelets were sampled on postoperative days 1, 2, 5, and 10. Logistic regression analysis was used to evaluate predictive capacity for coagulation-related complications.Results Overall, 380 patients were included (214 females, mean age 56 years); 38 patients had a history of thromboembolism and 57 were active smokers. Mean perioperative blood loss was 1228 mL and 231 (61%) received perioperative blood transfusions. PT-INR and APTT were elevated directly after surgery but returned to normal levels on postoperative day 5. Conversely, fibrinogen, platelet count, D-dimer, and antithrombin increased by postoperative day 5 and continued to increase up to day 10. There were 23 radiologically verified cases of VTE within 6 months. The multivariate analysis identified a completeness of cytoreduction score of 2-3 (p = 0.047) and day 2 D-dimer (p = 0.0082) as independent risk factors for postoperative VTE.Conclusion Significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery and elevated D-dimer on day 2 were independent risk factors for postoperative VTE.
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35.
  •  
36.
  • Dranichnikov, Paul, MD, PhD Candidate, 1980- (author)
  • HIPECology : Aspects of Postoperative Morbidity Following the HIPEC Procedure
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Peritoneal surface malignancy (PM), regardless of the dissemination site, was once considered a terminal condition.  However, the introduction of a surgical approach with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early intraperitoneal chemotherapy (EPIC) shifted the attitude from managing the symptoms of PM to disease treatment with curative intent. The magnitude of this combined therapy leaves the patients at risk for a diverse range of postoperative morbidities. Moreover, some small cohort studies argued that combining HIPEC with EPIC is associated with a higher risk of postoperative complications compared to HIPEC alone. The overall aim of the thesis was to investigate postoperative morbidity following the management of PM with CRS and HIPEC ± EPIC.We investigated readmission morbidity within 6 months after CRS and HIPEC, using a national population-based register. The results of this study showed that morbidity causing HIPEC-related readmission was higher than expected, with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and advanced age are independent predictors of morbidity and readmission. We analyzed postoperative coagulopathy and the risk for venous thromboembolic events (VTE) in a prospective study. Results revealed that significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery, and elevated D-dimer on day 2, were independent risk factors for postoperative VTE. Postoperative morbidity following HIPEC + EPIC was compared to morbidity following HIPEC alone in our propensity score matched study. Results showed that HIPEC + EPIC is associated with a prolonged hospital stay (LOS), but there was no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission. Finally, we also analyzed the impact of different strategies of intraoperative fluid management during CRS and HIPEC on postoperative outcomes. Goal-directed therapy (GDT) is associated with significantly improved LOS despite an increase in morbidity in some patients. GDT management does not affect the postoperative risk for hemorrhage, although the choice of an oxaliplatin-based HIPEC does. Personalized GDT based on patients’ characteristics and surgery should be utilized during the management of CRS and HIPEC patients.
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37.
  • Dranichnikov, Paul, MD, PhD Candidate, 1980-, et al. (author)
  • Morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases with or without early postoperative intraperitoneal chemotherapy : A propensity score matched study
  • 2022
  • In: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 48:7, s. 1598-1605
  • Journal article (peer-reviewed)abstract
    • Background: Combining hyperthermic intraperitoneal chemotherapy (HIPEC) treatment with early postoperative intraperitoneal chemotherapy (EPIC) may increase postoperative morbidity. This study aims to investigate postoperative morbidity after HIPEC+EPIC compared with HIPEC alone in patients with peritoneal metastases (PM).Materials and methods: This is a retrospective propensity score matched cohort study. All patients undergoing PM treatment at Uppsala University Hospital between February 2004 and December 2014 were included. Propensity score matching with a 1:1 ratio was performed using sex, primary tumor site, preoperative chemotherapy, peritoneal cancer index, completeness of cytoreduction score, and HIPEC regimen. Length of hospital stay, morbidity, reoperation rate, and readmission rate within 6 months were selected as endpoints.Results: A total of 390 consecutive patients were divided in two arms: HIPEC+EPIC (n = 115) and HIPEC alone (n = 275). The propensity score matching (n = 190) was successful with balanced covariates: 95 patients/arm. The length of stay (LOS) was longer in the HIPEC + EPIC group in the total cohort (30 vs 24 days, p < 0.001), with a trend towards significance in the propensity matched group (29 vs 25 days, p = 0.062). No other differences in endpoints were found.Conclusion: HIPEC+EPIC is associated with a prolonged hospital stay, but with no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission.
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38.
  • Dranichnikov, Paul, et al. (author)
  • Readmissions after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy-a national population-based study
  • 2020
  • In: World Journal of Surgical Oncology. - : BMC. - 1477-7819. ; 18:1
  • Journal article (peer-reviewed)abstract
    • Background Comprehensive readmission morbidity studies after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are scarce. This study aimed to investigate readmissions and in-hospital morbidity after CRS and HIPEC. Methods The national in-hospital patient register was used to identify patients via the HIPEC ICD code JAQ10 2004-2014. Data were retrieved from the index CRS/HIPEC treatment and from all HIPEC-related readmissions within 6 months. Univariate/multivariate logistical analyses were performed to identify risk factors for reinterventions and readmissions. Results A total of 519 patients (mean age 56 years) had a mean hospital stay of 27 days. Within 6 months, 150 readmissions for adverse events were observed in 129 patients (25%) with 67 patients requiring an intervention (13%). Totally 179 patients (34%) required a reintervention during the first 6 months with 85 (16%) requiring a reoperation. Of these 179 patients, 83 patients (46%) did not undergo the intervention at the HIPEC centre. Gastric resection was the only independent risk factor for in-hospital intervention, and advanced age for readmission. Conclusion Morbidity causing HIPEC-related readmission was higher than expected with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and high age are independent predictors of morbidity and readmission.
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39.
  • Dranichnikov, Paul, MD, PhD Candidate, 1980-, et al. (author)
  • The Impact on Postoperative Outcomes of Intraoperative Fluid Management Strategies During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
  • 2023
  • In: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 49:8, s. 1474-1480
  • Journal article (peer-reviewed)abstract
    • Background The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to investigate the impact of intraoperative fluid management strategy on postoperative outcomes and survival focusing on postoperative hemorrhage.  Methods 509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluids management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed. ResultsThe pre-GDT group received higher intraoperative fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p<0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p=0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p=0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p=0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p=0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p=0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p<0.0001). Survival did not differ between the groups.ConclusionWhile GDT management increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.  
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40.
  • Elias, Khalid, et al. (author)
  • Changes in bowel habits and patient-scored symptoms after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch
  • 2018
  • In: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289 .- 1878-7533. ; 14:2, s. 144-149
  • Journal article (peer-reviewed)abstract
    • 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.
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41.
  • Enblad, Malin (author)
  • Colorectal and appendiceal peritoneal metastases : From population studies to genetics
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • Peritoneal dissemination of colorectal and appendiceal origin was previously considered the end-stage of malignant disease. Today, treatment with cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) has prolonged survival and cured some patients with peritoneal metastases (PM). Unfortunately, a majority of patients still have fatal outcomes. In this thesis, colorectal and appendiceal PM were studied from a wide population-based perspective down to the detailed perspectives of histopathology and genetics, with the aim of further contributing to prolonged survival.In Paper I, the heterogeneous histopathology of PM was investigated and a substantial proportion of patients undergoing CRS and HIPEC were found to have surgical specimens lacking neoplastic epithelium. These patients had a favourable prognosis and the results illustrate the importance of thorough analysing and reporting of histopathology for understanding differences in survival outcomes and for improving patient selection. In Paper II, the role of inflammation in colorectal and appendiceal carcinogenesis was investigated at a population-based level. Patients with non-surgical treatment of appendicitis had an increased incidence of cancer (especially of appendiceal and right-sided colon cancer) compared to the general population. This should be taken into consideration in the discussion of optimal management of patients with appendicitis. In Paper III, risk factors for PM were studied with the aim of aiding in the detection of PM at earlier stages. Appendiceal and right-sided colon cancer, advanced tumour and node stages, mucinous histopathology and vascular invasion were identified as high risk features for developing PM, and should increase awareness of potential PM. In Paper IV, genome-wide chromosomal copy number alterations of PM were explored and associated with prognosis after CRS and HIPEC. Colorectal PM exhibited a wide range of alterations of which copy number gain on parts of chromosome 1p and 15q were significantly associated with poor prognosis and have the potential to be used as prognostic molecular markers in the future.In conclusion, this thesis provides new insights into the field of colorectal and appendiceal cancer and PM to be used for improved patient selection, early detection and prevention, ultimately contributing to improved survival.
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42.
  • Enblad, Malin, et al. (author)
  • Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases
  • 2019
  • In: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 26, s. 4835-4842
  • Journal article (peer-reviewed)abstract
    • Purpose: Genetic alterations in colorectal peritoneal metastases (PM) are largely unknown. This study was designed to analyze whole-genome copy number alterations (CNA) in colorectal PM and to identify alterations associated with prognosis after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)Methods: All patients with PM, originating from a colorectal adenocarcinoma, who were treated with CRS and HIPEC in Uppsala Sweden, between 2004 and 2015, were included (n = 114). DNA derived from formalin-fixed paraffin-embedded (FFPE) specimens were analyzed for CNA using molecular inversion probe arrays.Results: There were extensive but varying degrees of CNA, ranging from minimal CNA to total aneuploidy. In particular, gain of parts of chromosome 1p and major parts of 15q were associated with poor survival. A combination of gains of 1p and 15q was associated with poor survival, also after adjustment for differences in peritoneal cancer index and completeness of cytoreduction score [hazard ratio (HR) 5.96; 95% confidence interval (CI) 2.19-16.18]. These patients had a mean copy number (CN) of 3.19 compared with 2.24 in patients without gains. Complete CN analysis was performed in 53 patients. Analysis was unsuccessful for the remaining patients due to insufficient amounts of DNA and signals caused by interstitial components and normal cells. There was no difference in survival between patients with successful and unsuccessful CN analysis.Conclusions: This study shows that gains of parts of chromosome 1p and of major parts of chromosome 15q were significantly associated with poor survival after CRS and HIPEC, which could represent future prognostic biomarkers.
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43.
  • Enblad, Malin, et al. (author)
  • Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
  • 2016
  • In: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 23:4, s. 1149-1156
  • Journal article (peer-reviewed)abstract
    • 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.
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44.
  • Enblad, Malin, et al. (author)
  • Increased incidence of bowel cancer after non-surgical treatment of appendicitis
  • 2017
  • In: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 43:11, s. 2067-2075
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
45.
  • Enblad, Malin, et al. (author)
  • No Indication for Routine Resection of Surgical Scars during Cytoreductive Surgery and HIPEC
  • 2024
  • In: Cancers. - : MDPI. - 2072-6694. ; 16:11
  • Journal article (peer-reviewed)abstract
    • Background: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic impact of not undergoing routine scar resection.Method: All patients with previous surgery, treated with CRS and hyperthermic intraperitoneal chemotherapy, for colorectal PM or pseudomyxoma peritonei (PMP), at Uppsala University Hospital in 2013–2021, were included. Macroscopic SMs in surgical reports were compared with histopathological analyses.Results: In total, 227 patients were included. Among colorectal PM patients (n = 156), SM was macroscopically suspected in 41 (26%) patients, and 63 (40%) underwent scar resection. SM was confirmed in 19 (30%). Among patients with macroscopic suspicion, 45% had confirmed SM (positive predictive value, PPV). A total of 1 of 23 (4%) patients with no macroscopic suspicion had SM (negative predictive value, NPV = 96%). Among the PMP patients (n = 71), SM was macroscopically suspected in 13 (18%), and 28 (39%) underwent scar resection, of whom 12 (43%) had SM. The PPV was 77%. Occult SM was found in 1 of 14 (NPV = 93%). Not undergoing routine scar resection did not affect recurrence-free survival (RFS, p = 0.2) or overall survival (OS, p = 0.1) in colorectal PM patients or PMP patients (RFS p = 0.7, OS p = 0.7).Conclusion: Occult SM is uncommon and scar resection does not affect RFS or OS. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed upon suspicion or uncertainty.
  •  
46.
  • Enblad, Malin, et al. (author)
  • Omental metastases in patients with pseudomyxoma peritonei or colorectal peritoneal metastases - is routine omentectomy justified?
  • 2024
  • In: International Journal of Hyperthermia. - : Taylor & Francis. - 0265-6736 .- 1464-5157. ; 41:1
  • Journal article (peer-reviewed)abstract
    • Background: The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).Method: All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses.Results: In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses.Conclusion: OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.
  •  
47.
  •  
48.
  • Enblad, Malin, et al. (author)
  • Risk factors for appendiceal and colorectal peritoneal metastases
  • 2018
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 44:7, s. 997-1005
  • Journal article (peer-reviewed)abstract
    • BackgroundEarly 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.MethodsData 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.ResultsSynchronous 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.ConclusionsThis 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.
  •  
49.
  • Ezra, Emmanuel, et al. (author)
  • A short- and long-term follow-up study of intersphincteric NASHA Dx implants for fecal incontinence
  • 2022
  • In: Techniques in Coloproctology. - : Springer Nature. - 1123-6337 .- 1128-045X. ; 26:10, s. 813-820
  • Journal article (peer-reviewed)abstract
    • Background: The bulking agent NASHA Dx injected into the submucosal layer is effective in the treatment of fecal incontinence (FI) at short-and medium-term follow-up but efficacy after injection in the intersphincteric location is unknown. The aim of this study was to determine the short- and long-term efficacy and safety of NASHA Dx injected into the intersphincteric location for FI.Methods: Patients were recruited from referrals to our Department for treatment of FI in November 2008-January 2010. Eligible patients were injected with 8 ml of NASHA Dx. Patients with a subtotal treatment effect were retreated after 2-4 weeks. The change in number of fecal incontinence episodes, the proportion of responders defined as at least 50% decrease in number of FI episodes and side effects were the main outcome measures.Results: Sixteen patients, 15 women and 1 man with a median age of 68, 5 (range 44-80) years and a median CCFIS of 15 (range 10-19) were included in the study. The median number of incontinence episodes decreased from 21.5 (range 8-61) at baseline to 10 (range 0-30) at 6 months (p = 0.003) and 6 (range 0-44) at 12 months (p = 0.05). The median number of incontinence episodes in the 11 patients completing the 10-year follow-up was 26.5 (range 0-68). The percentage of responders at 12 months and 10 years were 56% and 27%, respectively. Mild to moderate pain at the injection site was described by 69%. There was one case of mild infection, successfully treated with antibiotics and one implant had to be removed due to dislocation.Conclusions: NASHA Dx as an intersphincteric implant improves incontinence symptoms in the short term with moderate side effects and can be used alone or as an adjunct to other treatment modalities. Long-term efficacy was observed in 27%.Keywords: Bulking agents; Fecal incontinence; Injection therapy; Pelvic floor.
  •  
50.
  • Ezra, Emmanuel, et al. (author)
  • Patterns of tined lead migration in sacral nerve modulation
  • 2020
  • In: International Journal of Colorectal Disease. - : SPRINGER. - 0179-1958 .- 1432-1262. ; 35:6, s. 1163-1166
  • Journal article (peer-reviewed)abstract
    • Aim Lead migration is a common cause of loss of efficacy in sacral nerve modulation. Our aim was to systematically study the migration pattern of tined leads in sacral nerve modulation. Our hypothesis was that tined leads may promote forward migration because of their configuration. Method Consecutive patients treated with sacral nerve modulation with a tined lead electrode, who had experienced loss of efficacy and had radiographs both at baseline and after loss of efficacy between 2005 and 2016 were eligible for inclusion. Results Twenty-five patients out of 70 with loss of efficacy were studied. Lead migration was measured as percent electrode movement in relation to sacral cortex at lateral projection. All had some degree of lead migration, ranging from 35% backward to 74% forward migration. Sixteen (64%) had forward migration while nine (36%) had backward migration. In seven patients (28%), loss of efficacy was associated with an episode of perceived mechanical strain on the electrode. Fifty percent (4/8) who associated their loss of efficacy with an adverse event had forward migration of the electrode. Conclusions Forward lead migration with concomitant loss of efficacy seems to be a common event in patients with tined leads, hence supporting our hypothesis. The retrospective design and that some of the patients with loss of efficacy could not be included because of incomplete data, which is a limitation to the study. Further studies are needed to confirm to what extent the direction and magnitude of the migration relate to loss of efficacy.
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