| 1. |
- Barot, Shabane, et al.
(författare)
-
Combined associations of a healthy lifestyle and body mass index with colorectal cancer recurrence and survival : a cohort study
- 2024
-
Ingår i: Cancer Causes and Control. - : Springer Nature. - 0957-5243 .- 1573-7225. ; 35:2, s. 367-376
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a healthy lifestyle and body mass index on prognosis following CRC diagnosis.METHODS: Treatment and follow-up data were collected from the patient files of 1098 participants from the Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards models adjusted for age, sex, and educational level.RESULTS: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score 4 (most healthy). Patients with the healthiest lifestyle (HL score 4) compared to the least healthy (HL score 0-1) had an improved recurrence-free survival (HL 4 vs HL 0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70).CONCLUSION: Adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC.
|
|
| 2. |
- Coorens, Maarten, et al.
(författare)
-
Innate lymphoid cell type 3-derived interleukin-22 boosts lipocalin-2 production in intestinal epithelial cells via synergy between STAT3 and NF-B
- 2019
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 294:15, s. 6027-6041
-
Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli and Klebsiella pneumoniae are opportunistic pathogens that are commonly associated with infections at mucosal surfaces, such as the lung or the gut. The host response against these types of infections includes the release of epithelial-derived antimicrobial factors such as lipocalin-2 (LCN-2), a protein that specifically inhibits the iron acquisition of Enterobacteriaceae by binding and neutralizing the bacterial iron-scavenging molecule enterobactin. Regulation of epithelial antimicrobial responses, including the release of LCN-2, has previously been shown to depend on IL-22, a cytokine produced by innate lymphoid cells type 3 (ILC3) during Enterobacteriaceae infections. However, much remains unknown about the extent to which antimicrobial responses are regulated by IL-22 and how IL-22 regulates the expression and production of LCN-2 in intestinal epithelial cells (IECs). Our study demonstrates how IL-22-induced activation of STAT3 synergizes with NF-B-activating cytokines to enhance LCN-2 expression in human IECs and elucidates how ILC3 are involved in LCN-2-mediated host defense against Enterobacteriaceae. Together, these results provide new insight into the role of ILC3 in regulating LCN-2 expression in human IECs and could prove useful in future studies aimed at understanding the host response against Enterobacteriaceae as well as for the development of antimicrobial therapies against Enterobacteriaceae-related infections.
|
|
| 3. |
- Dahlstrand, Ursula, et al.
(författare)
-
Costs Related to Diverting Ileostomy After Rectal Cancer Surgery: A Population-Based Healthcare Cost Analysis Based on Nationwide Registers
- 2023
-
Ingår i: Inquiry. - Thousand Oaks, CA : Sage Publications. - 0046-9580 .- 1945-7243. ; 60
-
Tidskriftsartikel (refereegranskat)abstract
- Low anterior resection for rectal cancer often includes a diverting loop-ileostomy to avoid the severe consequences of anastomotic leakage. Reversal of the stoma is often delayed, which can incur health-care costs on different levels. The aim is to, on population basis, determine stoma-related costs, and to investigate habitual and socioeconomic factors associated to the level of cost. Multi-register design with data from the Swedish Rectal Cancer Registry, the National Prescribed Drug Register, Statistics Sweden and cost-administrative data from the National Board of Health and Welfare. Data was gathered for 3564 patients with rectal cancer surgery 2007 to 2013, for 3 years following the surgery. Factors influencing the cost of inpatient care and stoma-related consumables were assessed with linear regression analyses. All monthly costs were higher for females (consumables P
|
|
| 4. |
- Djureinovic, Tatjana, et al.
(författare)
-
The CHEK2 1100delC variant in Swedish colorectal cancer
- 2006
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
|
|
| 5. |
- Forkel, Marianne, et al.
(författare)
-
Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers
- 2017
-
Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 47:8, s. 1280-1294
-
Tidskriftsartikel (refereegranskat)abstract
- Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44− ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.
|
|
| 6. |
- Ghazi, Sam, et al.
(författare)
-
Colorectal cancer susceptibility loci in a population-based study : associations with morphological parameters
- 2010
-
Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 177:6, s. 2688-2693
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.
|
|
| 7. |
- Gustafsson, Carl Pontus, et al.
(författare)
-
Loop-ileostomy reversal : patient-related characteristics influencing time to closure
- 2018
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 33:5, s. 593-600
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To identify factors associated with timing of stoma reversal after rectal cancer surgery in a large Swedish register-based cohort.METHODS: Three thousand five hundred sixty-four patients with rectal cancer who received a protective stoma during surgery in 2007-2013 were identified in the Swedish colorectal cancer register. Time to stoma reversal was evaluated over a follow-up period of one and a half years. Factors associated with timing of stoma reversal were analysed using Cox regression analysis. Reversal within 9 months (12 months if adjuvant chemotherapy) was considered latest expected time to closure.RESULTS: Stoma reversal was performed in 2954 (82.9%) patients during follow-up. Patients with post-secondary education had an increased chance for early stoma reversal (HR 1.13; 95% CI 1.02-1.25). Postoperative complications (0.67; 0.62-0.73), adjuvant chemotherapy (0.63; 0.57-0.69), more advanced cancer stage (stage III 0.74; 0.66-0.83 and stage IV 0.38; 0.32-0.46) and higher ASA score (0.80; 0.71-0.90 for ASA 3-4) were associated with longer time to reversal. Two thousand four hundred thirty-seven (68.4%) patients had stoma reversal within latest expected time to closure. Factors associated to decreased chance of timely reversal were more advanced cancer stage (stage III 0.64; 0.50-0.81 and stage IV 0.19; 0.13-0.27), postoperative complications (0.50; 0.42-0.59) and higher ASA score (0.77; 0.61-0.96 for ASA 3-4).CONCLUSIONS: Patients with a high level of education had a higher chance of timely reversal but medical factors had a stronger association to time to reversal. Patients with advanced rectal cancer are at high risk for non-reversal and should be considered for permanent stoma.
|
|
| 8. |
- Gustafsson, Pontus, et al.
(författare)
-
Higher Frequency of Anastomotic Leakage with Stapled Compared to Hand-Sewn Ileocolic Anastomosis in a Large Population-Based Study
- 2015
-
Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 39:7, s. 1834-1839
-
Tidskriftsartikel (refereegranskat)abstract
- The stapling technique was recommended in a recent Cochrane analysis based on relatively small randomized trials between 1970 and 2009. Data from a large Swedish population-based quality register were analyzed in order to compare the leakage frequency between stapled and hand-sewn ileocolic anastomoses in colon cancer surgery. Three-thousand four-hundred and twenty-eight patients with an ileocolic anastomosis were entered in a Swedish regional quality register for colon cancer, including the type of anastomosis used. The patients were analyzed by logistic regression regarding risk for leakage, and Cox proportional hazard regression for survival associated with the technique used for anastomosis. Analyses were made for gender, age, elective or emergency surgery, duration of surgery, bleeding, cancer stage, and local radicality. Most anastomoses were hand sewn (1,908 of 3,428, 55.7 %, p < 0.001), whereas stapling was more common among emergency cases (342 of 618, 55.3 %, p < 0.001). Clinically relevant leakage appeared in 58 patients (1.7 %), of whom 51 (87.9 %) were re-operated. Leakage was found to be more frequent after stapled anastomosis (2.4 vs. 1.2 %, p = 0.006), and in multivariate analysis, stapled anastomosis was the only risk factor (OR = 2.04 95 % CI 1.19-3.50). There was no difference in overall survival related to the technique. Hand-sewn anastomosis is not associated with a higher leakage rate when comparing to a stapling procedure and is recommended for routine and emergency right-sided colon cancer surgery. This recommendation is based on what appears to be a lower leakage rate, similar survival and lower material cost.
|
|
| 9. |
- Kokkinou, Efthymia, et al.
(författare)
-
CD45RA(+)CD62L(-) ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs
- 2022
-
Ingår i: Science immunology. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2470-9468. ; 7:70
-
Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naive-like ILCs suggests an ILC differentiation process that is akin to naive T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA(+) ILCs. CD45RA(+)CD62L(+) ILCs (CD62L(+) ILCs) resembled circulating naive ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA(+)CD62L(-) ILCs (CD62L(-) ILCs) were epigenetically similar to CD62L(+) ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L(+) and CD62L(-) ILCs contained uni- and multipotent precursors of ILC1s/NK cells and ILC3s. Differentiation of CD62L(+) and CD62L(-) ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L(-) ILCs with preferential differentiation capacity toward IL-22-producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L(+) and CD62L(-) ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.
|
|
| 10. |
- Konya, Viktoria, et al.
(författare)
-
Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells
- 2018
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 141:1, s. 279-292
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident group 3 innate lymphoid cells (ILC3s) play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy. Objective: We set out to define the role of 1 alpha,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL-23 plus Il-1 beta stimulation. Methods: Transcriptomes of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3 cytokine production, proliferation, and differentiation were determined by means of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions and ILC3s sorted from gut biopsy specimens of patients with IBD were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection. Results: ILC3s stimulated with IL-23 plus IL-1 beta upregulated the vitamin D receptor and responded to 1,25D with downregulation of the IL-23 receptor pathway. Consequently, 1,25D suppressed IL-22, IL-17F, and GM-CSF production from tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL-1 beta signaling pathway, as well as the IL-1 beta-inducible cytokines IL-6, IL-8, and macrophage inflammatory protein IL/1 beta. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in patients with IBD with active inflammation. Conclusion: In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.
|
|
