| 13111. |
- Olén, Ola, et al.
(författare)
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Colorectal cancer in ulcerative colitis : a Scandinavian population-based cohort study
- 2020
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 395:10218, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC.Methods: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account.Findings: During follow-up, we observed 1336 incident CRCs in the UC cohort (1.29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0.82 per 1000 person-years; HR 1.66, 95% CI 1.57-1.76). In the UC cohort, 639 patients died from CRC (0.55 per 1000 person-years), compared with 4451 reference individuals (0.38 per 1000 person-years; HR 1.59, 95% CI 1.46-1.72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0.0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1.54, 95% CI 1.33-1.78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1.38 (95% CI 1.20-1.60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1.25 (95% CI 1.03-1.51, or one additional case per 3041 patients with UC per 5 years).Interpretation: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines.
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| 13112. |
- Olinder, Jakob, et al.
(författare)
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Impact of breast density on diagnostic accuracy in digital breast tomosynthesis versus digital mammography : results from a European screening trial
- 2023
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Ingår i: Breast Cancer Research. - 1465-5411. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The diagnostic accuracy of digital breast tomosynthesis (DBT) and digital mammography (DM) in breast cancer screening may vary per breast density subgroup. The purpose of this study was to evaluate which women, based on automatically assessed breast density subgroups, have the greatest benefit of DBT compared with DM in the prospective Malmö Breast Tomosynthesis Screening Trial. Materials and methods: The prospective European, Malmö Breast Tomosynthesis Screening Trial (n = 14,848, Jan. 27, 2010–Feb. 13, 2015) compared one-view DBT and two-view DM, with consensus meeting before recall. Breast density was assessed in this secondary analysis with the automatic software Laboratory for Individualized Breast Radiodensity Assessment. DBT and DM’s diagnostic accuracies were compared by breast density quintiles of breast percent density (PD) and absolute dense area (DA) with confidence intervals (CI) and McNemar’s test. The association between breast density and cancer detection was analyzed with logistic regression, adjusted for ages < 55 and ≥ 55 years and previous screening participation. Results: In total, 14,730 women (median age: 58 years; inter-quartile range = 16) were included in the analysis. Sensitivity was higher and specificity lower for DBT compared with DM for all density subgroups. The highest breast PD quintile showed the largest difference in sensitivity and specificity at 81.1% (95% CI 65.8–90.5) versus 43.2% (95% CI 28.7–59.1), p <.001 and 95.5% (95% CI 94.7–96.2) versus 97.2% (95% CI 96.6–97.8), p < 0.001, respectively. Breast PD quintile was also positively associated with cancer detected via DBT at odds ratio 1.24 (95% CI 1.09–1.42, p = 0.001). Conclusion: Women with the highest breast density had the greatest benefit from digital breast tomosynthesis compared with digital mammography with increased sensitivity at the cost of slightly lower specificity. These results may influence digital breast tomosynthesis’s use in an individualized screening program stratified by, for instance, breast density. Trial registration. Trial registration at https://www.ClinicalTrials.gov : NCT01091545, registered March 24, 2010.
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| 13113. |
- Oliva, Delmy, 1967-, et al.
(författare)
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Individual genetic variation might predict acute skin reactions in women undergoing adjuvant breast cancer radiotherapy
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:12, s. 6763-6770
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Tidskriftsartikel (refereegranskat)abstract
- Adverse skin reactions during radiotherapy (RT) are common. The aim of this study was to explore whether genetic variation might be linked to acute radiation skin reactions (ARSR). Materials and Methods: One hundred and nineteen women undergoing adjuvant RT for breast cancer were included. The symptoms of itching, burning and irritation were self-reported twice using the visual analogue scale. Assessments used the Radiation Therapy Oncology Group scoring system for acute RT skin reaction (RTOG scale). Blood-based single nucleotide polymorphism (SNP) analysis was performed. Thirty SNPs of well-defined functional genes were investigated. Results: All women were assessed with ARSR. After RT, the women self-reported itching (n=97), burning (n=64) and irritation (n=96). Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. Conclusion: An association between two SNPs and ARSR was found. The possibility of using these SNPs as prognostic biomarkers for ARSR as tools to improve the care of patients needs further investigation.
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| 13114. |
- Oliva, Delmy, et al.
(författare)
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Opposing inflammatory biomarker responses to sleep disruption in cancer patients before and during oncological therapy
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSleep disruption is known to be highly prevalent in cancer patients, aggravated during oncological treatment and closely associated with reduced quality of life, therapeutic outcome and survival. Inflammatory factors are associated with sleep disruption in healthy individuals and cancer patients, but heterogeneity and robustness of inflammatory factors associated with sleep disruption and how these are affected by oncological therapy remain poorly understood. Furthermore, due to the complex crosstalk between sleep-, and therapy-associated factors, including inflammatory factors, there are currently no established biomarkers for predicting sleep disruption in patients undergoing oncological therapy. MethodsWe performed a broad screen of circulating biomarkers with immune-modulating or endocrine functions and coupled these to self-reported sleep quality using the Medical Outcomes Study (MOS) sleep scale. Ninety cancer patients with gastrointestinal, urothelial, breast, brain and tonsillar cancers, aged between 32 and 86 years, and scheduled for adjuvant or palliative oncological therapy were included. Of these, 71 patients were evaluable. Data was collected immediately before and again 3 months after onset of oncological therapy. ResultsSeventeen among a total of 45 investigated plasma proteins were found to be suppressed in cancer patients exhibiting sleep disruption prior to treatment onset, but this association was lost following the first treatment cycle. Patients whose sleep quality was reduced during the treatment period exhibited significantly increased plasma levels of six pro-inflammatory biomarkers (IL-2, IL-6, IL-12, TNF-a, IFN-g, and GM-CSF) 3 months after the start of treatment, whereas biomarkers with anti-inflammatory, growth factor, immune-modulatory, or chemokine functions were unchanged. ConclusionOur work suggests that biomarkers of sleep quality are not valid for cancer patients undergoing oncological therapy if analyzed only at a single timepoint. On the other hand, therapy-associated increases in circulating inflammatory biomarkers are closely coupled to reduced sleep quality in cancer patients. These findings indicate a need for testing of inflammatory and other biomarkers as well as sleep quality at multiple times during the patient treatment and care process.
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| 13115. |
- Oliva, Delmy, 1967-, et al.
(författare)
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Risk for relapse and death after adjuvant chemotherapy associated with SNPs in patients with breast cancer - A retrospective study
- 2022
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Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: For the women breast cancer (BC) patients included in this retrospective study, the first line of systemic treatment in adjuvant modality for breast cancer (BC) after surgery was fluorouracil, epirubicin and cyclophosphamide (FEC). The aim of our investigation was to analyze the prognostic biomarkers for relapse and death of patients eight to ten years after chemotherapy in association with nausea and vomiting.METHOD: This retrospective study included 114 patients treated between 2010 and 2013. Blood samples for Single Nucleotide Polymorphism (SNP) analysis before the chemotherapy treatment were collected. The medical records were used to determine relapses and death.RESULTS: Sixteen percent relapsed and 9 % died during the follow-up period. SNPs located in the genes ESR and CASP9 were associated with both relapse and death.CONCLUSIONS: Relapse and death were at a relative moderate level and consistent with other studies. Two SNPs in the Estrogen hormone receptor gene ESR1 and the apoptosis execution gene Caspases 9 (Casp9) were found to be associated with a higher risk of relapse and death. These findings suggest the possible value of blood biomarkers in the selection of individual treatments in the clinical setting.
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| 13116. |
- Oliva, Delmy, 1967-, et al.
(författare)
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Single nucleotide polymorphisms might influence chemotherapy induced nausea in women with breast cancer
- 2017
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier. - 2405-6308. ; 2, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background Women receiving FEC (5 fluorouracil, epirubicin and cyclophosphamide) chemotherapy (CT) for breast cancer (BC) often experience side effects such as nausea and vomiting. Individual variations of side effects occur in patients despite similar cancer therapy. The purpose of this study was to investigate a possible genetic background as a predictor for individual variations in nausea induced by CT. Methods 114 women were included in the study. All women received adjuvant CT for BC. Self-reported nausea and vomiting was recorded in a structured diary over ten days following treatment. Blood samples were collected before the treatment and used for the detection of 48 single nucleotide polymorphisms (SNPs) in 43 genes. SNPs from each individual woman were analyzed for their relation to the patient-reported frequency and intensity of nausea and vomiting. Results Eighty-four percent (n=96) of the women reported acute or delayed nausea or combined nausea and vomiting during the ten days following CT. Three out of the forty-eight SNPs in the following genes: FAS/CD95, RB1/LPAR6 and CCL2 were found to be associated with a risk of nausea. Conclusion SNPs in the FAS/CD95, RB1/LPAR6 and CCL2 genes were found to be associated with nausea among women treated with adjuvant FEC for BC. SNPs analysis is fast and cost effective and can be done prior to any cancer therapy. The association between individual SNPs and severe side effects from FEC may contribute to a more personalized care of patients with BC.
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| 13117. |
- Oliva, Delmy, 1967-, et al.
(författare)
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Variations in self-reported nausea, vomiting and well-being during the first 10 days postchemotherapy in women with breast cancer
- 2014
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Ingår i: Clinical Journal of Oncology Nursing. - Pittsburgh : Oncology Nursing Society. - 1092-1095 .- 1538-067X. ; 18:2, s. E32-E36
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Tidskriftsartikel (refereegranskat)abstract
- Women with breast cancer undergoing chemotherapy experience nausea and vomiting, both common symptoms affecting quality of life. The aim of the current study was to describe how nausea, vomiting, and well-being vary during the first 10 days after chemotherapy in women with breast cancer. A pilot study with a repeated-measurements design was conducted at a Swedish county hospital where 39 women with breast cancer treated with adjuvant chemotherapy were observed. A structured 10-day diary was used for data collection. Of the 39 women in the study, 33 experienced nausea and 6 also experienced vomiting after chemotherapy. Changes in well-being as a result of nausea or vomiting during any part of the day, as well as distress for other reasons, were reported. Well-being also varied among the individuals. The pattern of change in experienced levels of well-being was not homogeneous, nor did it move in any certain direction. The results of this study show that an individualized treatment approach is required to better meet individual women’s needs.
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| 13118. |
- Oliveira, Guilherme, et al.
(författare)
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EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE).
- 2017
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Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 470:5, s. 517-525
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Tidskriftsartikel (refereegranskat)abstract
- Carcinomas of the thyroid with Ewing family tumor element (CEFTEs) are small-cell thyroid tumors with epithelial differentiation that disclose p63 expression and EWSR1-FLI1 rearrangement, carry a favorable prognosis and may co-exist with papillary thyroid carcinoma (PTC) foci. Two histogenetic hypotheses have been advanced regarding the origin of CEFTEs: arising in PTCs or in solid cell nests (SCN). A total of 3 CEFTEs, 54 PTCs, and 10 SCNs were reviewed, and fluorescence in situ hybridization (FISH) technique was performed in all cases to search for the presence of EWSR1 rearrangements. The three CEFTEs disclosed the EWSR1-FLI1 rearrangement both in the small cell and in the PTC component. Out of the 54 PTC cases, 28 (51.9%) were positive, 20 (37.0%) were negative, and 6 (11.1%) were inconclusive for EWSR1 rearrangement; in two of the positive PTC cases, the EWSR1-FLI1 rearrangement was detected. Classic PTC disclosed more often the EWSR1 rearrangement than other PTC variants (p = 0.031). PTCs with EWSR1 rearrangement disclosed a lower percentage of nuclei with EWSR1 polysomy than those without EWSR1 rearrangement (p = 0.001). Out of the 10 SCNs, 7 (70.0%) were negative and 3 (30.0%) were inconclusive for the EWSR1 rearrangement. Monosomic nuclei were more frequent (mean of 44.3%) in SCNs than in PTCs (p < 0.001). The presence of the EWSR1-FLI1 rearrangement in PTC component of all studied CEFTEs and the existence of the EWSR1 rearrangement in some PTCs favor the origin of CEFTE from PTC. The high frequency of EWSR1 rearrangements in PTC may represent a new diagnostic marker of these tumors.
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| 13119. |
- Olm, Franziska, et al.
(författare)
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Label-free separation of neuroblastoma patient-derived xenograft (PDX) cells from hematopoietic progenitor cell products by acoustophoresis
- 2021
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Ingår i: Stem Cell Research & Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGraft-contaminating tumor cells correlate with inferior outcome in high-risk neuroblastoma patients undergoing hematopoietic stem cell transplantation and can contribute to relapse. Motivated by the potential therapeutic benefit of tumor cell removal as well as the high prognostic and diagnostic value of isolated circulating tumor cells from stem cell grafts, we established a label-free acoustophoresis-based microfluidic technology for neuroblastoma enrichment and removal from peripheral blood progenitor cell (PBPC) products.MethodsNeuroblastoma patient-derived xenograft (PDX) cells were spiked into PBPC apheresis samples as a clinically relevant model system. Cells were separated by ultrasound in an acoustophoresis microchip and analyzed for recovery, purity and function using flow cytometry, quantitative real-time PCR and cell culture.ResultsPDX cells and PBPCs showed distinct size distributions, which is an important parameter for efficient acoustic separation. Acoustic cell separation did not affect neuroblastoma cell growth. Acoustophoresis allowed to effectively separate PDX cells from spiked PBPC products. When PBPCs were spiked with 10% neuroblastoma cells, recoveries of up to 98% were achieved for PDX cells while more than 90% of CD34+ stem and progenitor cells were retained in the graft. At clinically relevant tumor cell contamination rates (0.1 and 0.01% PDX cells in PBPCs), neuroblastoma cells were depleted by more than 2-log as indicated by RT-PCR analysis of PHOX2B, TH and DDC genes, while > 85% of CD34+ cells could be retained in the graft.ConclusionThese results demonstrate the potential use of label-free acoustophoresis for PBPC processing and its potential to develop label-free, non-contact tumor cell enrichment and purging procedures for future clinical use.
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| 13120. |
- Olof Olsson, P., et al.
(författare)
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Inhibition of integrin αvβ6 changes fibril thickness of stromal collagen in experimental carcinomas
- 2018
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Ingår i: Cell Communication and Signaling. - : Springer Science and Business Media LLC. - 1478-811X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapeutic efficacy can be improved by targeting the structure and function of the extracellular matrix (ECM) in the carcinomal stroma. This can be accomplished by e.g. inhibiting TGF-β1 and -β3 or treating with Imatinib, which results in scarcer collagen fibril structure in xenografted human KAT-4/HT29 (KAT-4) colon adenocarcinoma. Methods: The potential role of αVβ6 integrin-mediated activation of latent TGF-β was studied in cultured KAT-4 and Capan-2 human ductal pancreatic carcinoma cells as well as in xenograft carcinoma generated by these cells. The monoclonal αVβ6 integrin-specific monoclonal antibody 3G9 was used to inhibit the αVβ6 integrin activity. Results: Both KAT-4 and Capan-2 cells expressed the αVβ6 integrin but only KAT-4 cells could utilize this integrin to activate latent TGF-β in vitro. Only when Capan-2 cells were co-cultured with human F99 fibroblasts was the integrin activation mechanism triggered, suggesting a more complex, fibroblast-dependent, activation pathway. In nude mice, a 10-day treatment with 3G9 reduced collagen fibril thickness and interstitial fluid pressure in KAT-4 but not in the more desmoplastic Capan-2 tumors that, to achieve a similar effect, required a prolonged 3G9 treatment. In contrast, a 10-day direct inhibition of TGF-β1 and -β3 reduced collagen fibril thickness in both tumor models. Conclusion: Our data demonstrate that the αVβ6-directed activation of latent TGF-β plays a pivotal role in modulating the stromal collagen network in carcinoma, but that the sensitivity to αVβ6 inhibition depends on the simultaneous presence of alternative paths for latent TGF-β activation and the extent of desmoplasia.
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