| 1. |
- Agger, Erik, et al.
(author)
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Negative prognostic impact of tumor deposits in rectal cancer – a national study cohort
- 2023
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In: Annals of Surgery. - 1528-1140. ; 273:3, s. 526-533
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Journal article (peer-reviewed)abstract
- Objective: To investigate whether tumor deposits (TDs) in rectal cancer are associated withincreased recurrence risk and decreased survival.Summary background data: Tumor deposits (TDs) are considered a risk factor forrecurrence after colon cancer resection and presence of TDs prompts adjuvant chemotherapy.The prognostic relevance of TDs in rectal cancer requires further exploration.Methods: All patients treated with abdominal resection surgery for rectal cancer in Swedenbetween 2011 and 2014 were eligible for inclusion in this retrospective cohort-study based onprospectively collected data from the Swedish ColoRectal Cancer Registry. Primary endpointwas local recurrence or distant metastasis. Secondary outcomes were overall and relativesurvival.Results: 5455 patients were identified. 3769 patients were analysed after exclusion. TDs werefound in 404 (10.7%) patients including where 140 (3.7%) patients with had N1c-status. InTD-positive patients, local recurrence and distant metastasis rates at 5 years were 6.3% [95%CI 3.8-8.8%] and 38.9% [95% CI, 33.6-43.5%] compared to 2.7% [95% CI, 2.1-3.3%] and14.3% [95% CI, 13.1-15.5%] in TD-negative patients. In multivariable regression analysis,risk of local recurrence and distant metastasis were increased; HR 1.86 [95% CI, 1.09-3.19;P=0.024] and 1.87 [95% CI, 1.52-2.31; P=was 68.8% [95% CI, 64.4-73.4%] in TD-positive patients and 80.7% [95% CI, 79.4-82.1%] inTD-negative patients. pN1c-patients had similar outcomes regarding local recurrence, distantCopyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of the article is prohibited.ACCEPTEDmetastasis and survival as pN1a-b stage patients. TD-positive pN1a-b patients hadsignificantly worse outcomes while TDs did not affect outcomes in pN2a-b patients.Conclusion: This study suggests that TDs have a negative impact on prognosis in rectalcancer. Thus, efforts should be made to diagnose TD-positive rectal cancer patientspreoperatively.
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| 2. |
- Agger, Erik, et al.
(author)
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Rektalcancer: : Risk för lokalt recidiv är beroende av RESEKTIONSMARGINAL
- 2020
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In: Onkologi i Sverige : den oberoende tidningen för svensk cancervård. - 1653-1582. ; 20:4, s. 27-32
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Journal article (pop. science, debate, etc.)abstract
- Rektalcancer är en sjukdom där behandlingsresultaten förbättrats kraftigt de senaste decennierna. Behandling för ändtarmscancer sker med antingen endast kirurgi eller kirurgi i kombination med onkologisk neoadjuvant behandling. Kirurgisk radikalitet, mikroskopisk marginal mellan tumörvävnad och frisk vävnad, är av stor betydelse för att minska risken för lokalrecidiv och öka överlevnaden
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| 3. |
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| 4. |
- Buchwald, Pamela
(creator_code:cre_t)
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Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries
- 2024
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In: British Journal of Surgery. - 1365-2168. ; 111:1
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Journal article (peer-reviewed)abstract
- Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks.Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned.Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31).Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov).
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| 5. |
- Jörgren, Fredrik, et al.
(author)
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Tumour deposits in colon cancer predict recurrence and reduced survival in a nationwide population-based study
- 2023
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In: BJS Open. - 2474-9842. ; 7:6
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Journal article (peer-reviewed)abstract
- Background: Tumour deposits are suggested to impact prognosis in colon cancer negatively. This study assessed the impact of tumour deposits on oncological outcomes.Methods: Data from the Swedish Colorectal Cancer Registry for patients who underwent R0 abdominal surgery for TNM stage I-III colon cancer between 2011 and 2014 with 5-year follow-up were analysed with multivariable analysis. Patients were categorized for their tumour deposit status and compared for the local recurrence and distant metastasis rates and 5-year survivals (overall and relative). Subgroup analyses were performed according to the nodal disease status.Results: Of 8146 stage I-III colon cancer patients who underwent R0 resection, 8014 patients were analysed (808 tumour deposits positive, 7206 tumour deposits negative). Patients with tumour deposits positive tumours had increased local recurrence and distant metastasis rates (7.2 versus 3.0 per cent; P < 0.001 and 33.9 versus 12.0 per cent; P < 0.001 respectively) and reduced 5-year overall and relative survival (56.8 per cent versus 74.9 per cent; P < 0.001 and 68.5 versus 92.6 per cent; P < 0.001 respectively). In multivariable analysis, tumour deposits moderately increased the risks of local recurrence and distant metastasis (hazard ratio 1.50, 95 per cent c.i. 1.09 to 2.07; P = 0.013 and HR 1.91, 95 per cent c.i. 1.64 to 2.23; P < 0.001 respectively) and worse 5-year overall and relative survival (hazard ratio 1.60, 95 per cent c.i. 1.40 to 1.82; P < 0.001 and excess hazard ratio 2.24, 95 per cent c.i. 1.81 to 2.78; P < 0.001 respectively). Subgroup analysis of N stages found that N1c patients had worse outcomes than N0 for distant metastasis and relative survival. For patients with lymph node metastases tumour deposits increased the risks of distant metastasis and worse overall and relative survival, except for N2b patients.Conclusion: Tumour deposits negatively impact the prognosis in colon cancer and must be considered when discussing adjuvant chemotherapy.
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| 6. |
- Lundström, Simon, et al.
(author)
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Adverse impact of tumor deposits in lymph node negative rectal cancer — a national cohort study
- 2023
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In: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 1432-1262. ; 38, s. 1-10
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Journal article (peer-reviewed)abstract
- Purpose This study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer. Methods Patients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node–negative rectal cancer. Results A total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72–6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35–2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86–4.11, p = 0.11]. Conclusion TDs are a negative predictor of DM and OS in lymph node–negative rectal cancer and could be taken into consideration when planning adjuvant treatment.
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| 7. |
- Nordén, Henrik, et al.
(author)
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Tumor Budding is a Weak Predictor of Oncological Outcomes in Colorectal Cancer: A Cohort Study
- 2024
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In: World Journal of Colorectal Surgery. - 1941-8213. ; 13:1, s. 17-22
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Journal article (peer-reviewed)abstract
- Background: Tumor budding (Bd) is a suggested risk factor for recurrence and decreased survival in colorectal cancer. Histopathological detection of Bd indicates increased invasive and migratory potential of the tumor cells.Objectives: This study aimed to explore the impact of Bd on oncological outcomes.Design: Retrospective cohort study.Patient and Methods: Patients treated with abdominal curative resection at Skåne University Hospital, Sweden, between 2017 and 2019 for colorectal adenocarcinoma were identified through the Swedish Colorectal Cancer Registry. Histopathological and medical records were reviewed retrospectively. Survival data were retrieved from the National Cause of Death registry.Main Outcome Measures: Primary outcomes were overall survival (OS), local recurrence (LR), and distant metastasis (DM) at 3 years.Sample Size: Seven hundred and sixty-eight patients were evaluated for inclusion. Two hundred and twenty-four patients were excluded due to stage 4 disease, early recurrence, or death within 90 days, R1/R2 resection, or missing histopathology regarding Bd.Results: Five hundred and forty-four patients were included for comparative analysis. One hundred and fifty-eight (29.0%) patients had histopathological signs of Bd. The mean follow-up was 33.8 (standard deviation, 6.6) months. Lymphovascular infiltration, tumor deposits, high tumor grade, and lymph node metastasis were prevalent in Bd-positive patients. Univariable Cox regression analysis showed decreased OS [hazard ratio (HR) = 2.30, 95% confidence interval (CI) = 1.30–3.31, P < 0.001] and increased DM (HR = 2.10, 95% CI = 1.32–3.34, P = 0.002), respectively. However, in multivariable Cox regression analysis, no significant results were observed: decreased OS (HR = 1.57, 95% CI = 0.95–2.59, P = 0.078) and DM (HR = 1.45, 95% CI = 0.86–2.47, P = 0.168). Bd was not associated with increased risk of LR.Conclusion: Bd was associated with other risk factors in colorectal cancer, which appear to be stronger prognostic indicators for oncological outcomes than Bd.Limitations: The study was limited by retrospective design. Three tier Bd-status was not provided for the entire study period.Conflict of Interest: The authors declare no financial or non-financial conflicts of interest.
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| 8. |
- Rasmussen, Eva Rye, et al.
(author)
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Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.
- 2020
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In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 20:6, s. 770-783
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Journal article (peer-reviewed)abstract
- Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.
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