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Rectal cancer: the influence of surgical technique on morbidity, mortality and survival
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0002-4950-2568
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2020. , p. 71
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2114
Keywords [en]
rectal cancer, anterior resection, high ligation, level of tie, anastomotic leakage, postoperative pain
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-176753ISBN: 978-91-7855-393-8 (print)ISBN: 978-91-7855-394-5 (electronic)OAI: oai:DiVA.org:umu-176753DiVA, id: diva2:1501399
Public defence
2020-12-11, Hörsal B, Unod T9, Umeå, 13:00 (English)
Opponent
Supervisors
Note

Serietillhörighet och delnummer saknas i publikationen.

Available from: 2020-11-20 Created: 2020-11-17 Last updated: 2020-12-10Bibliographically approved
List of papers
1. High arterial ligation and risk of anastomotic leakage in anterior resection for rectal cancer in patients with increased cardiovascular risk
Open this publication in new window or tab >>High arterial ligation and risk of anastomotic leakage in anterior resection for rectal cancer in patients with increased cardiovascular risk
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2015 (English)In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 11, p. 1018-1027Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Inferior mesenteric artery, total mesorectal excision, anastomotic insufficiency, neoplasm
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-110980 (URN)10.1111/codi.12971 (DOI)000362795400022 ()25851151 (PubMedID)2-s2.0-84943237718 (Scopus ID)
Available from: 2015-11-18 Created: 2015-11-02 Last updated: 2023-03-23Bibliographically approved
2. Population‐based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer
Open this publication in new window or tab >>Population‐based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer
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2019 (English)In: BJS Open, E-ISSN 2474-9842, Vol. 3, no 1, p. 106-111Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154649 (URN)10.1002/bjs5.50106 (DOI)000457222900012 ()30734021 (PubMedID)2-s2.0-85065768913 (Scopus ID)
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2023-03-23Bibliographically approved
3. Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer: A Nationwide Cohort Study
Open this publication in new window or tab >>Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer: A Nationwide Cohort Study
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2021 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 274, no 3, p. e236-e244Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wolters Kluwer, 2021
Keywords
level of tie, ligation level, mortality, rectal cancer, recurrence, survival
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:umu:diva-166887 (URN)10.1097/SLA.0000000000003663 (DOI)000683471400006 ()34397455 (PubMedID)2-s2.0-85114522928 (Scopus ID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2021-09-14Bibliographically approved
4. Early postoperative pain as a predictor of anastomotic leakage in colorectal cancer surgery
Open this publication in new window or tab >>Early postoperative pain as a predictor of anastomotic leakage in colorectal cancer surgery
(English)Manuscript (preprint) (Other academic)
Keywords
anastomotic insufficiency, leak, dehiscence, vital sign, colon, rectum
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-176752 (URN)
Available from: 2020-11-16 Created: 2020-11-16 Last updated: 2023-09-26

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