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- Hull, M, et al.
(författare)
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Obesity and colorectal cancer
- 2014
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 63:1, s. 205-205
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Lagergren, J, et al.
(författare)
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No association between colon cancer and adenocarcinoma of the oesophagus in a population based cohort study in Sweden
- 1999
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 44:6, s. 819-821
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports have indicated an association between Barrett’s metaplasia or adenocarcinoma of the oesophagus and colonic neoplasia, but the findings have been inconsistent. If true, such an association suggests common causal mechanisms.AIMSTo test the hypothesis of an association between Barrett’s metaplasia or adenocarcinoma of the oesophagus and colonic neoplasia.METHODSA population based, retrospective cohort study was performed on all Swedish patients with colon cancer diagnosed between 1958 and 1992. 538 500 person years at risk were reviewed among the 118 030 patients in the cohort (average follow up 4.6 years, median 2.1 years). The standardised incidence ratio (SIR), the ratio of the observed to the expected number of incident oesophageal adenocarcinomas, was used as a measure of relative risk. The expected number was derived from the entire Swedish population.RESULTSEleven oesophageal adenocarcinomas were found during follow up in the cohort, as against 9.5 expected (SIR=1.2; 95% confidence interval 0.6–2.1). Analysis by latency intervals after diagnosis of colon cancer showed no trend towards increasing or decreasing risk over time. There were no important sex differences in relative risk.CONCLUSIONSResults provide no support for a common link between colon cancer and oesophageal adenocarcinoma. Although the direct relation between colon cancer and Barrett’s oesophagus was not looked at, a search for common aetiological factors or genetic defects may not be fruitful. Screening for colonic neoplasia among patients with malignant or premalignant oesophageal mucosa, or vice versa, may not be warranted.
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- Turkington, RC, et al.
(författare)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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