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2.
  • Rutegård, Miriam, et al. (author)
  • PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study
  • 2019
  • In: Cancer Imaging. - : BMC. - 1740-5025 .- 1470-7330. ; 19
  • Journal article (peer-reviewed)abstract
    • PurposeThe role of hybrid imaging using F-18-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study.MethodsThis prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Vasterbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umea University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology.ResultsTwenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management.ConclusionsThe RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI.Trial registrationNCT03846882.
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  • Rutegård, Miriam, et al. (author)
  • Rectal cancer : a methodological approach to matching PET/MRI to histopathology
  • 2020
  • In: Cancer Imaging. - : BioMed Central (BMC). - 1740-5025 .- 1470-7330. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Purpose: To enable the evaluation of locoregional disease in the on-going RECTOPET (REctal Cancer Trial on PET/MRI/CT) study; a methodology to match mesorectal imaging findings to histopathology is presented, along with initial observations.Methods: FDG-PET/MRI examinations were performed in twenty-four consecutively included patients with rectal adenocarcinoma. In nine patients, of whom five received neoadjuvant treatment, a postoperative MRI of the surgical specimen was performed. The pathological cut-out was performed according to clinical routine with the addition of photo documentation of each slice of the surgical specimen, meticulously marking the location, size, and type of pathology of each mesorectal finding. This allowed matching individual nodal structures from preoperative MRI, via the specimen MRI, to histopathology.Results: Preoperative MRI identified 197 mesorectal nodal structures, of which 92 (47%) could be anatomically matched to histopathology. Of the matched nodal structures identified in both MRI and histopathology, 25% were found to be malignant. These malignant structures consisted of lymph nodes (43%), tumour deposits (48%), and extramural venous invasion (9%). One hundred eleven nodal structures (55%) could not be matched anatomically. Of these, 97 (87%) were benign lymph nodes, and 14 (13%) were malignant nodal structures. Five were malignant lymph nodes, and nine were tumour deposits, all of which had a short axis diameter < 5 mm.Conclusions: We designed a method able to anatomically match and study the characteristics of individual mesorectal nodal structures, enabling further research on the impact of each imaging modality. Initial observations suggest that small malignant nodal structures assessed as lymph nodes in MRI often comprise other forms of mesorectal tumour spread.Trial registration: Clinical Trials Identifier: NCT03846882.
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  • Back, Erik, et al. (author)
  • Mucosal blood flow in the remaining rectal stump is more affected by total than partial mesorectal excision in patients undergoing anterior resection : a key to understanding differing rates of anastomotic leakage?
  • 2021
  • In: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 406:6, s. 1971-1977
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Anterior resection is the procedure of choice for tumours in the mid and upper rectum. Depending on tumour height, a total mesorectal excision (TME) or partial mesorectal excision (PME) can be performed. Low anastomoses in particular have a high risk of developing anastomotic leakage, which might be explained by blood perfusion compromise. A pilot study indicated a worse blood flow in TME patients in an open setting. The aim of this study was to further evaluate perianastomotic blood perfusion changes in relation to TME and PME in a predominantly laparoscopic context.METHOD: In this prospective cohort study, laser Doppler flowmetry was used to evaluate the perianastomotic colonic and rectal perfusion before and after surgery. The two surgical techniques were compared in terms of mean differences of perfusion units using a repeated measures ANOVA design, which also enabled interaction analyses between type of mesorectal excision and location of measurement. Anastomotic leakage until 90 days after surgery was reported for descriptive purposes.RESULTS: Some 28 patients were available for analysis: 17 TME and 11 PME patients. TME patients had a reduced blood perfusion postoperatively compared to PME patients in the aboral posterior area (mean difference: -57 vs 18 perfusion units; p = 0.010). An interaction between mesorectal excision type and anterior/posterior location was detected at the aboral level (p = 0.007). Two patients developed a minor leakage, diagnosed after discharge.CONCLUSION: Patients operated on using TME have a decreased blood flow in the aboral posterior quadrant of the rectum postoperatively compared to patients operated on using PME. This might explain differing rates of anastomotic leakage.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02401100.
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  • Back, Erik, et al. (author)
  • Permanent stoma rates after anterior resection for rectal cancer : risk prediction scoring using preoperative variables
  • 2021
  • In: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 108:11, s. 1388-1395
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling.METHODS: Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk.RESULTS: Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive.CONCLUSION: Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.
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  • Bostrom, Petrus, et al. (author)
  • Arterial ligation in anterior resection for rectal cancer : A validation study of the Swedish Colorectal Cancer Registry
  • 2014
  • In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:7, s. 892-897
  • Journal article (peer-reviewed)abstract
    • Background: The level of arterial ligation has been a variable of the Swedish Colorectal Cancer Registry since 2007. The aim of this study is to evaluate the accuracy of this registry variable in relation to anterior resection for rectal cancer.Methods: The operative charts of all cardiovascularly compromised patients who underwent anterior resection during the period 2007-2010 in Sweden were retrieved and compared to the registry. We selected the study population to reflect the common assumption that these patients would be more sensitive to a compromised visceral blood flow. Levels of vascular ligation were defined, both oncologically and functionally, and their sensitivity, specificity, positive and negative predictive values, level of agreement and Cohen's kappa were calculated.Results: Some 744 (94.5%) patients were eligible for analysis. Functional high tie level showed a sensitivity of 80.2% and a specificity of 90.1%. Positive and negative predictive values were 87.7 and 83.8%, respectively. Level of agreement was 85.5% and Cohen's kappa 0.70. The corresponding calculations for oncologic tie level yielded similar results.Conclusion: The suboptimal validity of the Swedish Colorectal Cancer Registry regarding the level of vascular ligation might be problematic. For analyses with rare positive outcomes, such bowel ischaemia, or with minor expected differences in outcomes, it would be beneficial to collect data directly from the operative charts of the medical records in order to increase the chance of identifying clinically relevant differences.
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  • Boström, Petrus, et al. (author)
  • High arterial ligation and risk of anastomotic leakage in anterior resection for rectal cancer in patients with increased cardiovascular risk
  • 2015
  • In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 17:11, s. 1018-1027
  • Journal article (peer-reviewed)abstract
    • Aim: Controversy still exists as to whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage after anterior resection for rectal cancer. This population-based study was carried out to evaluate the independent association between high arterial ligation and anastomotic leakage in patients with increased cardiovascular risk.Method: All 2673 cases of registered anterior resection for rectal cancer from 2007 to 2010 were identified from the Swedish Colorectal Cancer Registry and cross-referenced with the Prescribed Drugs Registry, rendering a cohort of all patients with increased cardiovascular risk. Operative charts and registered data were reviewed for 722 patients. The association between high tie and anastomotic leakage, as quantified by ORs and 95% CIs, was evaluated in a logistic regression model, with adjustment for confounding, including assessment of interaction.Results: Symptomatic anastomotic leakage occurred in 12.3% (41/334) of patients in the high tie group and in 10.6% (41/388) in the low tie group. The use of high tie was not independently associated with a higher risk of anastomotic leakage (OR = 1.05; 95% CI: 0.61–1.84). In a post-hoc analysis, patients with a history of manifest cardiovascular disease and American Society of Anesthesiologists (ASA) score III–IV seemed to be at greater risk (OR = 3.66; 95% CI: 1.04–12.85).Conclusion: In the present population-based, observational setting, high tie was not independently associated with an increased risk of symptomatic anastomotic leakage after anterior resection for rectal cancer. However, this conclusion may not hold for patients with severe cardiovascular disease.
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  • Boström, Petrus, et al. (author)
  • Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer : A Nationwide Cohort Study
  • 2021
  • In: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:3, s. e236-e244
  • Journal article (peer-reviewed)abstract
    • Objective: The purpose of this study was to investigate the impact of tie level on oncological outcomes in rectal cancer surgery.Summary background data: Theoretically, a high tie of the inferior mesenteric artery could facilitate removal of apical node metastases and improve tumor staging accuracy. However, no appropriately sized randomized controlled trial exists and results from observational studies are not consistent.Methods: All stage I–III rectal cancer patients who underwent abdominal surgery with curative intention in 2007 to 2014 were identified and followed, using the Swedish Colorectal Cancer Registry. Primary outcome was cancer-specific survival, whereas overall and relative survival, locoregional and distant recurrence, and lymph node harvest were secondary outcomes, with high tie as exposure. We used propensity score matching to emulate a randomized controlled trial, and then performed Cox regression analyses to estimate hazard ratios (HRs) with confidence intervals (CIs).Results: Some 8287 patients remained for analysis, of which 37% had high tie surgery. After propensity score matching, the 5-year cancer-specific survival rate was overall 86% and we found no association between the level of tie and cancer-specific (HR 0.92, 95% CI 0.79–1.07) or overall (HR 0.98, 95% CI 0.89–1.08) survival, nor to locoregional (HR 0.85, 95% CI 0.59–1.23) or distant (HR 1.01, 95% CI 0.88–1.15) recurrence, nor to relative survival (HR 1.05, 95% CI 0.85–1.28). Stratification and sensitivity analyses were similarly insignificant, after adjustment for confounding. Total lymph node harvest was, however, increased after high tie surgery (P < 0.01), but no differences were seen regarding positive nodes (P = 0.72).Conclusion: In this nationwide cohort study, the level of tie did not influence any patient-oriented oncological outcome, neither overall nor in node-positive patients. This would allow the patient's anatomical configuration and the surgeon's preferences to determine the level of tie.
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  • Boström, Petrus, et al. (author)
  • Population‐based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer
  • 2019
  • In: BJS Open. - : John Wiley & Sons. - 2474-9842. ; 3:1, s. 106-111
  • Journal article (peer-reviewed)abstract
    • Background: Anastomotic leakage following anterior resection for rectal cancer may result in death. The aim of this study was to yield an updated, population‐based estimate of postoperative mortality and evaluate possible interacting factors.Methods: This was a retrospective national cohort study of patients who underwent anterior resection between 2007 and 2016. Data were retrieved from a prospectively developed database. Anastomotic leakage constituted exposure, whereas outcome was defined as death within 90 days of surgery. Logistic regression analyses, using directed acyclic graphs to evaluate possible confounders, were performed, including interaction analyses.Results: Of 6948 patients, 693 (10·0 per cent) experienced anastomotic leakage and 294 (4·2 per cent) underwent reintervention due to leakage. The mortality rate was 1·5 per cent in patients without leakage and 3·9 per cent in those with leakage. In multivariable analysis, leakage was associated with increased mortality only when a reintervention was performed (odds ratio (OR) 5·57, 95 per cent c.i. 3·29 to 9·44). Leaks not necessitating reintervention did not result in increased mortality (OR 0·70, 0·25 to 1·96). There was evidence of interaction between leakage and age on a multiplicative scale (P = 0·007), leading to a substantial mortality increase in elderly patients with leakage.Conclusion: Anastomotic leakage, in particular severe leakage, led to a significant increase in 90‐day mortality, with a more pronounced risk of death in the elderly.
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  • Boström, Petrus, 1981- (author)
  • Rectal cancer : the influence of surgical technique on morbidity, mortality and survival
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • Surgery is still the most common treatment for rectal cancer, being the most effective and cost-efficient modality. However, it is not without risk, nor without controversies. This dissertation is an evaluation of the pros and cons of high versus low ligation, whether anastomotic leakage is still prevalent after surgery and associated with increased mortality, and if the risk of leakage could be predicted by early postoperative pain.Study I relied upon case records and registry data to evaluate the causal effect of high ligation on the risk of anastomotic leakage after anterior resection in 722 patients with increased cardiovascular risk. When controlling for confounders, no association was found overall. However, an increased risk for leakage after high ligation was noted for the few patients who suffered from both manifest cardiovascular disease and ASA III–IV (OR 3.66, 95% CI 1.04–12.85) and when performed in a low volume hospital (OR 3.89, 95% 1.58– 9.59). Study II estimated the risk of anastomotic leakage and death after anterior resection today. Among the 6,948 patients, 10.0% suffered from leakage, in whom mortality was 3.9% versus 1.5% for patients without a leak. However, this increased mortality was driven entirely by patients in need of reintervention, who exhibited a 7.5% 90-day mortality, resulting in a significantly increased risk (OR 5.57, 95% CI 3.29–9.44), when controlling for confounders, while conservatively treated leakage was not associated with mortality. Age acted as an effect modifier, as postoperative mortality after leakage was increased in the elderly.Study III returned to high versus low ligation as exposure, to evaluate the long-term oncological benefits of either ligation level, with cancer-specific survival as primary outcome. The final cohort of 8,287 patients who underwent abdominal surgery for rectal cancer, with curative intent, was followed for a minimum of 3.5 years. After propensity score matching, no significant differences were found between high and low ligation for any survival or recurrence analysis, nor in the unmatched cohort, when controlling for confounders. A statistically significant difference was found for lymph node harvest, which was slightly greater in high ligation (17.7 vs 16.7 lymph nodes). Finally, study IV estimated the independent predictive ability of postoperative pain, measured on the numerical rating scale (NRS), on the risk for anastomotic leakage after colorectal cancer surgery. It seems as if increased early pain is an independent predictor for leakage (OR 1.73, 95% CI 1.22– 2.46 for NRS 4–10), with increasing risk of leakage with increasing pain (OR 2.42 for NRS 8–10). In addition, increased pain was more strongly associated with more severe leakage.In summary, the level of ligation seems to be of importance only in a select group of high-risk patients, but offers no obvious oncological advantages. The high incidence and serious sequelae of anastomotic leakage makes it one of the most important clinical challenges in colorectal surgery, with especially detrimental effects in the elderly. A better understanding of the causal pathways behind leakage, and the overall harm and benefit of ligation level and diverting stomas, might allow a better selection of treatment for future patients.
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  • Grahn, Oskar, et al. (author)
  • Postoperative non-steroidal anti-inflammatory drugs in relation to recurrence, survival and anastomotic leakage after surgery for colorectal cancer
  • 2022
  • In: Colorectal Disease. - : Blackwell Publishing. - 1462-8910 .- 1463-1318. ; 24:8, s. 933-942
  • Journal article (peer-reviewed)abstract
    • AIM: To investigate whether non-steroidal anti-inflammatory drugs (NSAIDs) could be beneficial or harmful when used perioperatively for colorectal cancer patients, as inflammation may affect occult disease and anastomotic healing.METHODS: This is a protocol-based retrospective cohort study on colorectal cancer patients operated between 2007 and 2012 at 21 hospitals in Sweden. The NSAID exposure was retrieved from postoperative analgesia protocols, while outcomes and patient data were retrieved from the Swedish Colorectal Cancer Registry. Older or severely comorbid patients, as well as those with disseminated or non-radically operated tumours were excluded. Multivariable regression with adjustment for confounders was performed, estimating hazard ratios (HRs) for long-term and odds ratios (ORs) for short-term outcomes, including 95% confidence intervals (CIs).RESULTS: Some 6945 patients remained after exclusion, of which 3996 were treated at hospitals where an NSAID protocol was in place. No association was seen between NSAIDs and recurrence-free survival (HR 0.97; 95% CI 0.87-1.09). However, a reduction in cancer recurrence was detected (HR 0.83; 95% 0.72-0.95), which remained significant when stratifying into locoregional (HR 0.68; 95% CI 0.48-0.97) and distant recurrences (HR 0.85; 95% CI 0.74-0.98). Anastomotic leakage was less frequent (HR 0.69%; 95% CI 0.51-0.94) in the NSAID-exposed, mainly due to a risk reduction in colo- and ileo-rectal anastomoses (HR 0.47; 95% CI 0.33-0.68).CONCLUSION: There was no association between NSAID exposure and recurrence-free survival, but an association with improved cancer recurrence and the rate of anastomotic leakage was detected, which may depend on tumour site and anastomotic location.
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  • Holmgren, Klas, et al. (author)
  • Anterior resection for rectal cancer in Sweden : validation of a registry-based method to determine long-term stoma outcome
  • 2018
  • In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:12, s. 1631-1638
  • Journal article (peer-reviewed)abstract
    • Background: A permanent stoma after anterior resection for rectal cancer is common. Nationwide registries provide sufficient power to evaluate factors influencing this phenomenon, but validation is required to ensure the quality of registry-based stoma outcomes.Methods: Patients who underwent anterior resection for rectal cancer in the Northern healthcare region of Sweden between 1 January 2007 and 31 December 2013 were reviewed by medical records and followed until 31 December 2014 with regard to stoma outcome. A registry-based method to determine nationwide long-term stoma outcomes, using data from the National Patient Registry and the Swedish Colorectal Cancer Registry, was developed and internally validated using the chart reviewed reference cohort. Accuracy was evaluated with positive and negative predictive values and Kappa values. Following validation, the stoma outcome in all patients treated with an anterior resection for rectal cancer in Sweden during the study period was estimated. Possible regional differences in determined stoma outcomes between the six Swedish healthcare regions were subsequently evaluated with the χ2 test.Results: With 312 chart reviewed patients as reference, stoma outcome was accurately predicted through the registry-based method in 299 cases (95.8%), with a positive predictive value of 85.1% (95% CI 75.8%-91.8%), and a negative predictive value of 100.0% (95% CI 98.4%-100.0%), while the Kappa value was 0.89 (95% CI 0.82-0.95). In Sweden, 4768 patients underwent anterior resection during the study period, of which 942 (19.8%) were determined to have a permanent stoma. The stoma rate varied regionally between 17.8-29.2%, to a statistically significant degree (p = .001).Conclusion: Using data from two national registries to determine long-term stoma outcome after anterior resection for rectal cancer proved to be reliable in comparison to chart review. Permanent stoma prevalence after such surgery remains at a significant level, while stoma outcomes vary substantially between different healthcare regions in Sweden.
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  • Holmgren, Klas, et al. (author)
  • Defunctioning stomas may reduce chances of a stoma-free outcome after anterior resection for rectal cancer
  • 2021
  • In: Colorectal Disease. - : Blackwell Publishing. - 1462-8910 .- 1463-1318. ; 23:11, s. 2859-2869
  • Journal article (peer-reviewed)abstract
    • AIM: To investigate the conflicting consequences of faecal diversion on stoma outcomes and anastomotic leakage in anterior resection for rectal cancer, including interaction effects determined by the extent of mesorectal excision.METHOD: Anterior resections between 2007 and 2016 were identified using the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine stoma outcome 2 years after surgery. Tumour distance from the anal verge constituted a proxy for extent of mesorectal excision [total mesorectal excision (TME): ≤10 cm; partial mesorectal excision (PME): 13-15 cm]. With confounder-adjusted probit regression, the total effect of defunctioning stoma on permanent stoma, and the interaction effect of extent of mesorectal excision, were estimated together with the indirect effect through anastomotic leakage. Baseline risks, risk differences (RDs) and relative risks (RRs) were reported.RESULTS: The main study cohort included 4529 patients. Defunctioning stomas influenced the absolute permanent stoma risk (TME: RD 0.11 [95% CI 0.09-0.13]; PME: RD 0.15 [95% CI 0.13-0.16]). The baseline risk was higher in TME, with a resulting greater RR in PME (2.23 [95% CI 1.43-3.02] vs 4.36 [95% CI 3.05-5.68]). The indirect reduction in permanent stoma rates, due to the alleviating effect of faecal diversion on anastomotic leakage, was small (TME: 0.89 [95% CI 0.81-0.96]; PME: 0.96 [95% CI 0.91-1.00]).CONCLUSION: In anterior resection for rectal cancer, defunctioning stomas may reduce chances of a stoma-free outcome. Considering leakage reduction benefits, consequences of routine diversion in TME might be fairly balanced, while this seems questionable in PME.
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  • Holmgren, Klas, et al. (author)
  • High stoma prevalence and stoma reversal complications following anterior resection for rectal cancer : a population-based multicentre study
  • 2017
  • In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 19:12, s. 1067-1075
  • Journal article (peer-reviewed)abstract
    • AIM: Fashioning a defunctioning stoma is common when performing an anterior resection for rectal cancer in order to avoid and mitigate the consequences of an anastomotic leakage. We investigated the permanent stoma prevalence, factors influencing stoma outcome and complication rates following stoma reversal surgery.METHOD: Patients who had undergone an anterior resection for rectal cancer between 2007 and 2013 in the northern healthcare region were identified using the Swedish Colorectal Cancer Registry and were followed until the end of 2014 regarding stoma outcome. Data were retrieved by a review of medical records. Multiple logistic regression was used to evaluate predefined risk factors for stoma permanence. Risk factors for non-reversal of a defunctioning stoma were also analysed, using Cox proportional-hazards regression.RESULTS: A total of 316 patients who underwent anterior resection were included, of whom 274 (87%) were defunctioned primarily. At the end of the follow-up period 24% had a permanent stoma, and 9% of patients who underwent reversal of a stoma experienced major complications requiring a return to theatre, need for intensive care or mortality. Anastomotic leakage and tumour Stage IV were significant risk factors for stoma permanence. In this series, partial mesorectal excision correlated with a stoma-free outcome. Non-reversal was considerably more prevalent among patients with leakage and Stage IV; Stage III patients at first had a decreased reversal rate, which increased after the initial year of surgery.CONCLUSION: Stoma permanence is common after anterior resection, while anastomotic leakage and advanced tumour stage decrease the chances of a stoma-free outcome. Stoma reversal surgery entails a significant risk of major complications.
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18.
  • Holmgren, Klas, 1989- (author)
  • Permanent stoma after anterior resection for rectal cancer : prevalence and mechanisms
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • While sphincter-saving surgery constitutes standard treatment for rectal cancer, anterior resection still harbours a significant risk of a permanent stoma in the long run. Although anastomotic leakage plays a major role in this surgical dilemma, the exact mechanisms are not known, while surveys indicate a stoma-free outcome is essential for a majority of patients. To address this issue, the overall aim of the present thesis was to investigate the permanent stoma prevalence in patients undergoing anterior resection for rectal cancer in Sweden, and to identify plausible mechanisms that impede prospects of a stoma-free outcome.In a population-based cohort, chart review of patients who had anterior resection for rectal cancer in the Northern healthcare region in Sweden between 2007 and 2013 showed that 75 out of 316 (24%) patients ended up with a permanent stoma. Of 274 patients (87%) primarily defunctioned with a stoma, 229 underwent stoma closure, 21 (9%) of whom suffered major complications that required return to theatre or worse. A permanent stoma was shown to be more common among patients with anastomotic leakage and an advanced tumour stage.A registry-based method to estimate nationwide stoma outcome after anterior resection for rectal cancer was developed, using data from the Swedish Colorectal Cancer Registry and the National Patient Registry. With a chart-reviewed cohort as reference, stoma outcome was assessed with a positive predictive value of 85.1%, and a negative predictive value of 100.0%. In patients operated in Sweden between 2007 and 2013, the registry-based method determined that 942 out of 4768 (19.8%) had a permanent stoma, while stoma rates varied substantially between different healthcare regions.In a 1:1 matched case-control study of 82 patients who had curative resection for non-disseminated colorectal cancer, a subgroup analysis of 34 patients with rectal cancer displayed biomarker aberrations in serum measured preoperatively in those with anastomotic leakage. Compared to complication-free controls, 15 proteins related to inflammation were elevated, of which two (C-X-C motif chemokine 6, and C-C motif chemokine 11) remained significant after adjustment for multiple testing.Based on a cohort of 4529 patients who had anterior resection, tumour height served as a proxy to determine the extent of mesorectal excision, while long-term stoma outcome was classified using a previously validated registry-based method. Defunctioning stomas significantly decreased chances of a stoma-free outcome, especially in patients undergoing partial mesorectal excision; for these patients, faecal diversion was also least beneficial in terms of reducing anastomotic leakage.In conclusion, every fifth patient undergoing anterior resection for rectal cancer in Sweden eventually ends up with a permanent stoma. Although construction of a defunctioning stoma decreases the risk of symptomatic anastomotic leakage, subsequent takedown surgery carries a substantial risk of major complications, while chances of a long-term stoma-free outcome become significantly reduced. To facilitate selective use of faecal diversion, novel markers to identify high-risk anastomoses prior to surgery have been identified, but require validation in larger prospective settings. Anterior resection without a defunctioning stoma should be considered in appropriately informed patients for whom a stoma-free outcome is of importance. In particular, this holds true for patients eligible for partial mesorectal excision, where anastomotic dehiscence is less frequent and the advantageous effects of a defunctioning stoma are limited.
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20.
  • Holmgren, Klas, et al. (author)
  • Preoperative biomarkers related to inflammation may identify high-risk anastomoses in colorectal cancer surgery : explorative study
  • 2022
  • In: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:3
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Colorectal anastomotic leakage can be considered a process of failed wound healing, for which related biomarkers might be a promising research area to decrease leak rates.METHODS: Patients who had elective surgery with a primary anastomosis for non-metastatic colorectal cancer, at two university hospitals between 1 January 2010 and 31 December 2015 were included. Patients with an anastomotic leak were identified and matched (1:1) to complication-free controls on the basis of sex, age, tumour stage, tumour location, and operating hospital. Preoperative blood samples were analysed by use of protein panels associated with systemic or enteric inflammation by proteomics, and enzyme-linked immunosorbent assays. Multivariable projection methods were used in the statistical analyses and adjusted for multiple comparisons to reduce false positivity. Rectal cancer tissue samples were evaluated with immunohistochemistry to determine local expression of biomarkers that differed significantly between cases and controls.RESULTS: Out of 726 patients undergoing resection, 41 patients with anastomotic leakage were matched to 41 controls. Patients with rectal cancer with leakage displayed significantly elevated serum levels of 15 proteins related to inflammation. After controlling for a false discovery rate, levels of C-X-C motif chemokine 6 (CXCL6) and C-C motif chemokine 11 (CCL11) remained significant. In patients with colonic cancer with leakage, levels of high-sensitivity C-reactive protein (hs-CRP) were increased before surgery. Local expression of CXCL6 and CCL11, and their receptors, were similar in rectal tissues between cases and controls.CONCLUSION: Patients with anastomotic leakage could have an upregulated inflammatory response before surgery, as expressed by elevated serological levels of CXCL6 and CCL11 for rectal cancer and hs-CRP levels in patients with colonic cancer respectively.
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22.
  • Kverneng Hultberg, Daniel, et al. (author)
  • Level of vascular tie and its effect on functional outcome 2 years after anterior resection for rectal cancer
  • 2017
  • In: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 19:11, s. 987-995
  • Journal article (peer-reviewed)abstract
    • Aim Previous research indicates that high tie of the inferior mesenteric artery during anterior resection for rectal cancer might be associated with an increased risk of postoperative functional disturbances. The goal of this population-based retrospective cohort study was to further investigate that association.Method Patients who underwent anterior resection for rectal cancer from April 2011 to September 2012 were identified through the Swedish Colorectal Cancer Registry. Bowel and urogenital function were assessed by a postal questionnaire 2 years after surgery. Information on the level of mesenteric tie and clinical variables was retrieved from the registry. The outcome was defined as any defaecatory, urinary or sexual dysfunction as reported by the patient. The association between high tie and the outcome was evaluated with multivariable logistic and linear regression with adjustment for confounders, such as sex, body mass index, comorbidity and preoperative radiation.Results With a response rate of 86%, 805 patients were included in the study. Of these, 46% were operated with high tie. After adjustment for confounders, high tie did not affect the risk of faecal incontinence (OR 0.85; 95% CI 0.59-1.22), urinary incontinence (OR 0.94; 95% CI 0.63-1.41) or various aspects of sexual dysfunction (erectile dysfunction, anejaculation, dyspareunia and coital vaginal dryness). However, an association between high tie and defaecation at night was detected (OR 1.44; 95% CI 1.02-2.03).Conclusion This study does not support that the level of vascular tie influences the risk of major defaecatory, urinary or sexual disturbances 2 years after anterior resection for rectal cancer.
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23.
  • Kverneng Hultberg, Daniel, et al. (author)
  • Nonsteroidal anti-inflammatory drugs and the risk of anastomotic leakage after anterior resection for rectal cancer
  • 2017
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:10, s. 1908-1914
  • Journal article (peer-reviewed)abstract
    • Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in colorectal surgery due to their opioid-sparing effect. However, several studies have indicated an increased risk of anastomotic leakage following NSAID treatment, although conflicting results exist. The primary goal of this study was to further examine whether postoperative NSAIDs are independently associated with anastomotic leakage after anterior resection for rectal cancer. Methods: Patients who underwent anterior resection for rectal cancer during 2007-2013 in 15 different hospitals in three healthcare regions in Sweden were included in the study. Registry data and information from patient records were retrieved. The association between NSAID treatment (for at least two days in the first postoperative week) and symptomatic anastomotic leakage (within 90 days) was evaluated with multiple logistic regression, with adjustment for pertinent confounding factors. Results: Some 1495 patients were included in the study. Of these, 27% received postoperative NSAIDs for at least two days in the first postoperative week. Symptomatic anastomotic leakage occurred in 11% and 14% in the NSAID and non-NSAID group, respectively. With adjustment for confounders, the odds ratio for leakage among patients who received NSAIDs compared with those who did not was 0.88 (95% CI 0.65-1.20). No differences were seen between non-selective and COX-2-selective NSAIDs. Conclusion: Postoperative NSAID treatment does not seem to increase the risk of symptomatic anastomotic leakage after anterior resection for rectal cancer. NSAID use appears to be safe, but a well-powered randomized clinical trial is warranted. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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24.
  • Kverneng Hultberg, Daniel, 1990- (author)
  • Surgery for rectal cancer : the impact of perioperative factors
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • Rectal cancer is one of the most common and deadly cancer forms worldwide. A large proportion of rectal cancer patients are surgically treated with curative intention, with anterior resection being the most frequently used method today. During surgery, the inferior mesenteric artery is either ligated proximal (high tie) or distal to the left colic artery (low tie). It is not known whether the tie level affects the oncologic nor the functional outcome. Postoperatively, about one in ten patients develop an anastomotic leakage. It is unclear whether treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) affects the risk of leakage, or whether having a leakage influences the functional outcome. The general aims of this dissertation were to increase the knowledge of intra- and postoperative treatment for rectal cancer, with the goal of improving the oncologic and functional outcomes, as well as reducing postoperative complications. National registers, predominantly the Swedish Colorectal Cancer Registry, were used in all of the dissertation’s four retrospective cohort studies to identify and retrieve information regarding patients. Various statistical methods have been used in all studies with the aim of eliminating bias, including confounding.In Study I, high tie slightly increased the total number of harvested lymph nodes in the included 8287 patients, as compared with low tie, while the primary outcome cancer-specific survival, as well as secondary oncologic outcomes, were not affected. This indicates that the oncologic outcome does not have to be considered when the surgeon determines the level of tie.In Study II, investigating the effect of tie level on the functional outcome, the outcome was any defecatory or urogenital symptoms two years after anterior resection, assessed with a mailed questionnaire. With a response rate of 86%, 805 patients were included. High tie did not, except for increasing the need of defecation at night, influence the risk of major dysfunction. Again, this would facilitate the choice of tie level.Study III used the same outcome, and in part the same study population, as Study II, but instead with the exposure anastomotic leakage. With a response rate of 82%, 1180 patients were included. We found that anastomotic leakage increased the risk of reduced sexual activity and increased the use of aid products for fecal incontinence after anterior resection, while the risk of urinary incontinence was unexpectedly decreased. Other outcomes were not clearly affected. In Study IV, in addition to the register, information was gathered from patient records. In the included 1495 patients who had undergone anterior resection, postoperative NSAID treatment was not found to increase the risk of symptomatic anastomotic leakage. There were no differences between non-selective and COX-2 selective NSAIDs. This study does not support that NSAID treatment increases the risk of anastomotic leakage after such surgery.
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25.
  • Kverneng Hultberg, Daniel, et al. (author)
  • The Impact of Anastomotic Leakage on Long-Term Function after Anterior Resection for Rectal Cancer
  • 2020
  • In: Diseases of the Colon & Rectum. - : American Society of Colon & Rectal Surgeons. - 0012-3706 .- 1530-0358. ; 63:5, s. 619-628
  • Journal article (peer-reviewed)abstract
    • Background: It is still not clear whether anastomotic leakage after anterior resection for rectal cancer affects long-term functional outcome.Objective: To evaluate how anastomotic leakage following anterior resection for rectal cancer influences defecatory, urinary and sexual function.Design: In this retrospective population-based cohort study, patients were identified through the Swedish Colorectal Cancer Registry, which was also used for information on the exposure variable anastomotic leakage, and covariates.Settings: A nationwide register was used for including patients.Patients: All patients undergoing anterior resection for rectal cancer in Sweden from April 2011– June 2013 were included.Main Outcome Measures: Outcome was any defecatory, sexual or urinary dysfunction, assessed two years after surgery by a postal questionnaire. The association between anastomotic leakage and function was assessed in multivariable logistic and linear regression models, with adjustment for confounding.Results: Response rate was 82%, resulting in 1180 included patients. Anastomotic leakage occurred in 7.5%. A permanent stoma was more common among leak patients (44% vs. 9%; p<0.001). Leakage patients had an increased risk of aid use for fecal incontinence (OR 2.27; 95% CI 1.20-4.30) and reduced sexual activity (90% vs. 82%; p=0.003), while the risk of urinary incontinence was decreased (OR 0.53; 95% CI 0.31-0.90). A sensitivity analysis assuming that a permanent stoma was created due to anorectal dysfunction strengthened the negative impact of leakage on defecatory dysfunction.Limitations: Limitations include the used questionnaire not having been previously validated, underreporting of anastomotic leakage in the register, and small patient numbers in the analysis of sexual symptoms.Conclusions:a Anastomotic leakage was found to statistically significantly increase the risk of aid use due to fecal incontinence and reduced sexual activity, though the impact on defecatory dysfunction might be underestimated, as permanent stomas are sometimes fashioned due to anorectal dysfunction. Further research is warranted, especially regarding urogenital function.
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26.
  • Rutegård, Jörgen, 1943-, et al. (author)
  • Non-steroidal anti-inflammatory drugs in colorectal surgery : a risk factor for anastomotic complications?
  • 2012
  • In: World Journal of Gastrointestinal Surgery. - : Baishideng Publishing Group Co., Limited. - 1948-9366. ; 4:12, s. 278-280
  • Journal article (peer-reviewed)abstract
    • In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.
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27.
  • Rutegård, Martin, et al. (author)
  • Anastomotic leakage in rectal cancer surgery : The role of blood perfusion
  • 2015
  • In: World Journal of Gastrointestinal Surgery. - : Baishideng Publishing Group Inc.. - 1948-9366. ; 7:11, s. 289-292
  • Journal article (other academic/artistic)abstract
    • Anastomotic leakage after anterior resection for rectal cancer remains a common and often devastating complication. Preoperative risk factors for anastomotic leakage have been studied extensively and are used for patient selection, especially whether to perform a diverting stoma or not. From the current literature, data suggest that perfusion in the rectal stump rather than in the colonic limb may be more important for the integrity of the colorectal anastomosis. Moreover, available research suggests that the mid and upper rectum is considerably more vascularized than the lower part, in which the posterior compartment seems most vulnerable. These data fit neatly with the observation that anastomotic leaks are far more frequent in patients undergoing total compared to partial mesorectal excision, and also that most leaks occur dorsally. Clinical judgment has been shown to ineffectively assess anastomotic viability, while promising methods to measure blood perfusion are evolving. Much interest has recently been turned to near-infrared light technology, enhanced with fluorescent agents, which enables intraoperative perfusion assessment. Preliminary data are promising, but large-scale controlled trials are lacking. With maturation of such technology, perfusion measurements may in the future inform the surgeon whether anastomoses are at risk. In high colorectal anastomoses, anastomotic revision might be feasible, while a diverting stoma could be fashioned selectively instead of routinely for low anastomoses.
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28.
  • Rutegård, Martin, et al. (author)
  • Anterior Resection for Rectal Cancer and Visceral Blood Flow : An Explorative Study
  • 2016
  • In: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 105:2, s. 78-83
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: Impaired blood perfusion may be implicated in anastomotic leakage after anterior resection for rectal cancer. We investigated whether high ligation of the inferior mesenteric artery or total mesorectal excision compromises visceral blood flow in the colonic limb and the rectal stump, respectively.MATERIAL AND METHODS: A prospective cohort study was conducted in a university hospital setting. We used Laser Doppler flowmetry to evaluate the impact of level of tie on colonic limb perfusion and the extent of the mesorectal excision on the rectal blood flow. In the rectum, different quadrants were also assessed. The Mann-Whitney U test was used to compare mean blood flow ratios between groups.RESULTS: Some 23 patients were recruited in a convenience sample during a period in 2012-2013. The mean blood flow ratio was not decreased after high tie compared to low tie surgery (1.71 vs 1.19; p = 0.28). Total mesorectal excision reduced the mean blood flow ratio in the rectum, as compared with partial mesorectal excision (0.76 vs 1.28; p = 0.14). This was especially pronounced in the posterior aspect of the rectum (0.66 vs 1.68; p = 0.02).CONCLUSION: High tie ligation did not seem to decrease colonic limb perfusion, while total mesorectal excision may decrease rectal blood flow. The posterior quadrant of the rectum might be particularly vulnerable to the dissection involved in total mesorectal excision.
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29.
  •  
30.
  • Rutegård, Martin, et al. (author)
  • Current use of diverting stoma in anterior resection for cancer : population-based cohort study of total and partial mesorectal excision
  • 2016
  • In: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 31:3, s. 579-585
  • Journal article (peer-reviewed)abstract
    • Purpose A diverting stoma is commonly used to reduce the risk of anastomotic leakage when performing total mesorectal excision (TME) in anterior resection for rectal cancer. The purpose of this study was to evaluate the impact of fecal diversion in relation to partial mesorectal excision (PME).Methods A retrospective analysis was undertaken on a national cohort, originally created to study the impact of central arterial ligation on patients with increased cardiovascular risk. Some 741 patients operated with anterior resection for rectal cancer during the years 2007 through 2010 were followed up for 53 months. Multivariate logistic regression was used to evaluate the impact of diverting stoma on the risk of anastomotic leakage and permanent stoma, expressed as odds ratios (ORs) and 95 % confidence intervals (CIs).Results The risk of anastomotic leakage was increased in TME surgery when not using a diverting stoma (OR 5.1; 95 % CI 2.2-11.6), while the corresponding risk increase in PME patients was modest (OR 1.8; 95 % CI 0.8-4.0). At study completion or death, 26 and 13 % of TME and PME patients, respectively, had a permanent stoma. A diverting stoma was a statistically significant risk factor for a permanent stoma in PME patients (OR 4.7; 95 % CI 2.5-9.0), while less important in TME patients (OR 1.8; 95 % CI 0.6-5.5).Conclusion The benefit of a diverting stoma concerning anastomotic leakage in this patient group seems doubtful. Moreover, the diverting stoma itself may contribute to the high rate of permanent stomas.
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31.
  • Rutegård, Martin, 1982-, et al. (author)
  • Defunctioning loop ileostomy in anterior resection for rectal cancer and subsequent renal failure : nationwide population-based study
  • 2023
  • In: BJS Open. - : Oxford University Press. - 2474-9842. ; 7:3
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking.METHODS: This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported.RESULTS: A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes.CONCLUSION: Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.
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32.
  • Rutegård, Martin, 1982-, et al. (author)
  • Early postoperative mortality after surgery for rectal cancer in Sweden, 2000-2011
  • 2014
  • In: Colorectal Disease. - : Wiley-Blackwell. - 1462-8910 .- 1463-1318. ; 16:6, s. 426-432
  • Journal article (peer-reviewed)abstract
    • Aim: Postoperative mortality has traditionally been defined as death within 30 days of surgery. Such mortality after rectal cancer resection has declined significantly during the last decades. However, it is possible that this decline can be explained merely by a shift towards an increase in 90-day mortality.Method: A nationwide cohort study was based on data from the Swedish Colorectal Cancer Registry and the Swedish Patient Registry concerning patients who had undergone surgical resection for rectal cancer in 2000-2011. Unconditional logistic regression was used to calculate ORs with 95% CIs regarding mortality in different calendar periods (2000-2003, 2004-2007 and 2008-2011) in two different postoperative time periods (0-30 days and 31-90 days).Results: Some 15,437 patients were included in this surgical cohort. Mortality within 30 days of surgery decreased from 2.1% in 2000-2003 to 1.6% in 2008-2011, whilst the corresponding mortality within the 31- to 90-day time window decreased from 2.1% to 1.4%. The adjusted risk of 30-day mortality in 2008-2011 was statistically significantly decreased compared with that in 2000-2003 (OR = 0.67; 95% CI: 0.48-0.93) and mortality in the 31- to 90-day time window was also reduced for 2008-2011 compared with 2000-2003 (OR = 0.71; 95% CI: 0.51-0.99).Conclusion: This population-based, nationwide Swedish study indicates that postoperative mortality, as measured within 30 days and 31-90 days after surgery, has decreased with time. However, no relevant shift from earlier to later postoperative mortality was discerned.
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33.
  • Rutegård, Martin, et al. (author)
  • Efficiency of Colorectal Cancer Surveillance in Patients With Ulcerative Colitis : 38 Years' Experience in a Patient Cohort From a Defined Population Area
  • 2017
  • In: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 106:2, s. 133-138
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program.MATERIAL AND METHODS: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10 years.RESULTS: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10 years, 2.0% at 20 years, 3.0% at 30 years, and 9.4% at 40 years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42-5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients.CONCLUSION: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.
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34.
  • Rutegård, Martin, 1982-, et al. (author)
  • High tie in anterior resection for rectal cancer confers no increased risk of anastomotic leakage
  • 2012
  • In: British Journal of Surgery. - Malden, MA : Wiley-Blackwell. - 0007-1323 .- 1365-2168. ; 99:1, s. 127-132
  • Journal article (peer-reviewed)abstract
    • Background: It is controversial whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage, especially in the elderly and unfit. This population-based study was carried out to evaluate the independent association between a high arterial ligation and anastomotic leakage in anterior resection for rectal cancer. Methods: All patients who had anterior resection for rectal cancer from 2007 to 2009 inclusive were identified in the Swedish Colorectal Cancer Registry. The association between high tie and anastomotic leakage was evaluated in a logistic regression model, with adjustment for confounders. Stratification was performed for co-morbidity as judged by the American Society of Anesthesiologists (ASA) classification. Results: Symptomatic anastomotic leakage occurred in 81 (9.9 per cent) of 818 patients with a high tie and 108 (9.8 per cent) of 1101 without. Overall, the use of a high tie was not associated with a higher risk of anastomotic leakage (odds ratio (OR) 1.00, 95 per cent confidence interval 0.72 to 1.39). There was no increased risk in patients classifed as ASA grade I or II (OR 0.97, 0.69 to 1.35), or in those graded ASA III or IV (OR 1.26, 0.58 to 2.75). Conclusion: In the present population-based setting, use of a high tie was not associated with an increased rate of symptomatic anastomotic leakage.
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35.
  • Rutegård, Martin, 1982-, et al. (author)
  • Multicentre, randomised trial comparing acellular porcine collagen implant versus gluteus maximus myocutaneous flap for reconstruction of the pelvic floor after extended abdominoperineal excision of rectum : study protocol for the Nordic Extended Abdominoperineal Excision (NEAPE) study
  • 2019
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:5
  • Journal article (peer-reviewed)abstract
    • Introduction: Different surgical techniques are used to cover the defect in the floor of the lesser pelvis after an ‘extralevator’ or ‘extended’ abdominoperineal excision for advanced rectal cancer. However, these operations are potentially mutilating, and the reconstruction method of the pelvic floor has been studied only sparsely. We aim to study whether a porcine-collagen implant is superior or equally beneficial to a gluteus maximus myocutaneous flap as a reconstruction method.Methods and analysis: This is a multicentre non-blinded randomised controlled trial with the experimental arm using a porcine-collagen implant and the control arm using a gluteus maximus muscle and skin rotation flap. Considered for inclusion are patients with rectal cancer, who are operated on with a wide abdominoperineal rectal excision including most of the levator muscles and where the muscle remnants cannot be closed in the midline with sutures. Patients with a primary or recurrent rectal cancer with an estimated survival of more than a year are eligible. The randomisation is computer generated with a concealed sequence and stratified by participating hospital and preoperative radiotherapy regimen. The main outcome is physical performance 6 months after surgery measured with the timed-stands test. Secondary outcomes are perineal wound healing, surgical complications, quality of life, ability to sit and other outcomes measured at 3, 6 and 12 months after surgery. To be able to state experimental arm non-inferiority with a 10% margin of the primary outcome with 90% statistical power and assuming 10% attrition, we aim to enrol 85 patients from May 2011 onwards.Ethics and dissemination: The study has been approved by the Regional Ethical Review board at Umeå University (protocol no: NEAPE-2010-335-31M). The results will be disseminated through patient associations and conventional scientific channels.
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36.
  • Rutegård, Martin, et al. (author)
  • Non-Steroidal Anti-Inflammatory Drug Use and Risk of Anastomotic Leakage after Anterior Resection : A Protocol-Based Study
  • 2016
  • In: Digestive Surgery. - : S. Karger AG. - 0253-4886 .- 1421-9883. ; 33:2, s. 129-135
  • Journal article (peer-reviewed)abstract
    • Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been introduced as opioid-sparing analgesics in colorectal surgery. However, recent research has implicated these drugs as risk factors for anastomotic dehiscence.Methods: The Swedish Colorectal Cancer Registry was used to identify all patients operated with anterior resection for rectal cancer at centres that performed more than 25 abdominal operations per year, from 2007 to 2012, inclusive. The registry provided individual patient data on demographic variables and symptomatic anastomotic leakage. The patient exposure to NSAIDs was defined according to the protocol of the hospital at which the patient was operated. Logistic regression was employed to estimate ORs and 95% CIs, adjusting for confounders.Results: The study cohort comprised 2,605 patients operated at 21 centres. In the NSAID group, 102/1,458 (7.0%) suffered an anastomotic leak, as compared to 124/1,023 (10.8%) in the non-NSAID group. With adjustment for confounding, patients treated at NSAID hospitals had a reduced risk of developing anastomotic leakage (OR 0.68; 95% CI 0.48-0.96).Conclusions: In this retrospective protocol-based study, NSAIDs did not increase the risk of anastomotic leakage after anterior resection for rectal cancer. The postoperative use of NSAIDs may not be detrimental, but more research is warranted.
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37.
  • Sörelius, Karl, 1981-, et al. (author)
  • A nationwide study on the incidence of mesenteric ischaemia after surgery for rectal cancer demonstrates an association with high arterial ligation
  • 2019
  • In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 21:8, s. 925-931
  • Journal article (peer-reviewed)abstract
    • Aim: The incidence of mesenteric ischaemia after resection for rectal cancer has not been investigated in a population-based setting. The use of high ligation of the inferior mesenteric artery might cause such ischaemia, as the bowel left in situ depends on collateral blood supply after a high tie.Method: The Swedish Colorectal Cancer Registry was used to identify all patients subjected to an abdominal resection for rectal cancer during the years 2007-2017 inclusive. Mesenteric ischaemia within the first 30 postoperative days was recorded, classified as either stoma necrosis or colonic necrosis. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for mesenteric ischaemia in relation to high tie, with adjustment for confounding.Results: Some 14 657 patients were included, of whom 59 (0.40%) had a reoperation for any type of mesenteric ischaemia, divided into 34 and 25 cases of stoma necrosis and colonic necrosis, respectively. Compared with patients who did not require reoperation for mesenteric ischaemia following rectal cancer surgery, the proportion having high tie was greater (54.2% vs 38.5%; P = 0.032). The adjusted OR for reoperation due to any mesenteric ischaemia with high tie was 2.26 (95% CI 1.34-3.79), while the corresponding estimates for stoma and colonic necrosis, respectively, were 1.60 (95% CI 0.81-3.17) and 3.69 (95% CI 1.57-8.66).Conclusion: The incidence of reoperation for mesenteric ischaemia after abdominal resection for rectal cancer is low, but the use of a high tie might increase the risk of colonic necrosis demanding surgery.
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38.
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39.
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40.
  • Boström, Petrus, et al. (author)
  • Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery
  • 2021
  • In: International Journal of Colorectal Disease. - : Springer-Verlag New York. - 0179-1958 .- 1432-1262. ; 36:9, s. 1955-1963
  • Journal article (peer-reviewed)abstract
    • Purpose: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage.Methods: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data.Results: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome.Conclusion: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.
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41.
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42.
  • Cook, Michael B., et al. (author)
  • Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma : a study within the National Cancer Institute Cohort Consortium
  • 2019
  • In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 68:6, s. 960-968
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.DESIGN: This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.RESULTS: Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.CONCLUSION: This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.
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43.
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44.
  • 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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45.
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46.
  • Gadan, Soran, et al. (author)
  • Defunctioning stoma and short- and long-term outcomes after low anterior resection for rectal cancer : a nationwide register-based cohort study
  • 2021
  • In: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 36:7, s. 1433-1442
  • Journal article (peer-reviewed)abstract
    • PURPOSE: A defunctioning stoma reduces the risk of symptomatic anastomotic leakage after low anterior resection for rectal cancer and mitigates the consequences when a leakage occurs, but the impact on mortality and oncological outcomes is unclear. The aim was to investigate the associations of a defunctioning stoma with short- and long-term outcomes in patients undergoing low anterior resection for rectal cancer.METHODS: Data from all patients who underwent curative low anterior resection for rectal cancer between 1995 and 2010 were obtained from the Swedish Colorectal Cancer Register. A total of 4130 patients, including 2563 with and 1567 without a defunctioning stoma, were studied. Flexible parametric models were used to estimate hazard ratios for all-cause mortality, 5-year local recurrence, and distant metastatic disease in relation to the use of defunctioning stoma, adjusting for confounding factors and accounting for potential time-dependent effects.RESULTS: During a median follow-up of 8.3 years, a total of 2169 patients died. In multivariable analysis, a relative reduction in mortality was observed up to 6 months after surgery (hazard ratio = 0.82: 95% CI 0.67-0.99), but not thereafter. After 5 years of follow-up, 4.2% (173/4130) of the patients had a local recurrence registered and 17.9% (741/4130) had developed distant metastatic disease, without difference between patients with and without defunctioning stoma.CONCLUSION: A defunctioning stoma is associated with a short-term reduction in all-cause mortality in patients undergoing low anterior resection for rectal cancer without any difference in long-term mortality and oncological outcomes, and should be considered as standard of care.
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47.
  • Gadan, Soran, 1976- (author)
  • Long term aspects of defunctioning stoma following low anterior resection for rectal cancer
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • In Sweden, more than 2 000 individuals are diagnosed with rectal cancer each year. Surgery is the main curative treatment, and involves removal of the tumor with the surrounding mesorectum in adefined anatomical plane. Intestinal continuity is restored by anastomosing the colon to the rectalstump at the pelvic floor. Leakage of the anastomosis is a potentially life-threatening complication, and is most common in low anastomoses located at the pelvic floor. A temporary defunctioning loop stoma (DS) reduces both the rate of leakage and the severity when leakage occurs despite DS. The use of DS has increased substantially in Sweden over the last 15 years, especially in low anastomoses at the level of the pelvic floor. The purpose of this thesis was to increase the understanding of different aspects of DS and its impact on anorectal function, long-term survival, cancer recurrence, timing of stoma reversal, and the risk of having a permanent stoma.In Paper I, the LARS score questionnaire was used to assess anorectal function among patients who had participated in a Swedish nationwide randomized trial. Those who had a DS (n=116) were compared to those without DS (n=118). After a median follow-up time of 12 years, patients with DS had a poorer bowel function than those without DS in terms of incontinence for gas and loose stools. No differences were found with regard to fecal incontinence, defragmentation, and urgency. Women and patients who had received preoperative radiotherapy had poorer anorectal function. Impaired anorectal function was associated with lower self-perceived health.In Paper II, a cohort of 110 patients from Örebro Region, Sweden, was investigated with regard to whether or not the DS was reversed within a 4-month period. Only 25% had their stoma reversed within this timeframe. Moreover, a third of the patients had a delayed stoma closure without any identifiable medical reason. This was an improvement compared to a previous study from the same region, which found that 58% of patients operated between 1995 and 2007 had a delayed stoma reversal without any identifiable medical reason. The most common cause for delayed DS reversal in our study was adjuvant chemotherapy (38%).In Paper III, the impact of DS on long-term survival and local and distant cancer recurrence was investigated in a nationwide population-based study cohort operated with low anterior resection (LAR) between 1995 and 2010 (n=4130), retrieved from the Swedish Colorectal Cancer Registry. Patients with a DS at LAR (n=2163) had an increased survival rate during the first 3 years afterindex surgery in comparison with those without a DS. Beyond 3 years of follow-up, no difference was noted between the two groups. There were no differences regarding either local cancer recurrence or distant metastases between patients with and without DS.In Paper IV, the risk of having a permanent stoma beyond 5 years after rectal cancer surgery was evaluated in 232 patients (excluding mortality within 90 days; n=2) previously randomized to DS or no DS. After a median follow-up of 15 years, 25% (57/232) had a permanent stoma. Of these, 23% (13/57) had their permanent stoma constructed at median 10 years after the index surgery. The incidence of permanent stoma was numerically lower in the group originally randomized to DS, but this difference was not statistically significant. Anastomotic leakage was the most common riskfactor for ending up with a permanent stoma.
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48.
  • Gadan, S., et al. (author)
  • What is the risk of permanent stoma beyond 5 years after low anterior resection for rectal cancer? : A 15-year follow-up of a randomized trial
  • 2020
  • In: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 22:12, s. 2098-2104
  • Journal article (peer-reviewed)abstract
    • Aim: Low anterior resection of the rectum for cancer (LAR) entails a risk of symptomatic anastomotic leakage as well as impaired anorectal function, both of which may eventually result in the need for a permanent stoma (PS). The aim was to investigate the incidence of and risk factors for PS beyond 5 years following LAR.Methods: Patients undergoing LAR and included in a multicentre trial with randomization to defunctioning stoma or not were followed for a median of 15 years. The reasons for a PS up to 5 years (PS <= 5 years) and beyond 5 years (PS > 5 years) were identified and compared. Risk factors for PS were analysed.Results: Of all patients, 25% (57/232) had a PS. PS <= 5 years occurred in 19% (44/232) at a median of 12.5 months and PS > 5 years in 6% (13/232) at a median of 118 months following LAR. The main reason for PS <= 5 years was impaired anorectal function in 55% (24/44) and the main reason for PS > 5 years was pelvic sepsis related to the colorectal anastomosis in 46% (6/13). The major risk factor for PS was symptomatic anastomotic leakage, which occurred in 56% (32/57) of patients with PS and 10% (17/175) of patients without PS (P < 0.001).Conclusion: One-fourth of the patients who ended up with a PS had it fashioned beyond 5 years at a median of 10 years following LAR. Symptomatic anastomotic leakage was the major risk factor for PS, and impaired anorectal function was the main overall reason for a PS.
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49.
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50.
  • Gerdin, Anders, et al. (author)
  • Preoperative beta blockers and other drugs in relation to anastomotic leakage after anterior resection for rectal cancer
  • 2024
  • In: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 26:5, s. 974-986
  • Journal article (peer-reviewed)abstract
    • Aim: Previous research has indicated that preoperative beta blocker therapy is associated with a decreased risk of complications after surgery for rectal cancer. This is thought to arise because of the anti-inflammatory activity of the drug. These results need to be reproduced and analyses extended to other drugs with such properties, as this information might be useful in clinical decision-making. The main aim of this work was to replicate previous findings of beta blocker use as a prognostic marker for postoperative leakage. We also investigated whether drug exposure might induce anastomotic leaks.Method: This is a retrospective multicentre cohort study, comprising 1126 patients who underwent anterior resection for rectal cancer between 2014 and 2018. The use of any preoperative beta blocker was treated as the primary exposure, while anastomotic leakage within 12 months of surgery was the outcome. Secondary exposures comprised angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins and metformin. Using multivariable regression, we performed a replication analysis with a predictive aim for beta blockers only, while adjustment for confounding was done in more causally oriented analyses for all drugs. We estimated incidence rate ratio (IRR) and relative risk (RR) with 95% confidence intervals (CIs).Results: Anastomotic leakage occurred in 20.6% of patients. Preoperative beta blockers were used by 22.7% of the cohort, while the leak distribution was almost identical between exposure groups. In the main replication analysis, no association could be detected (IRR 0.95, 95% CI 0.68–1.33). In the causally oriented analyses, only metformin affected the risk of leakage (RR 1.59, 95% Cl 1.31–1.92).Conclusion: While previous research has suggested that preoperative beta blocker use could be prognostic of anastomotic leakage, this study could not detect any such association. On the contrary, our results indicate that preoperative beta blocker use neither predicts nor causes anastomotic leakage after anterior resection for rectal cancer.
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