| 11. |
- Carlsson, Göran, 1951, et al.
(författare)
-
Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia.
- 2012
-
Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 158:3, s. 363-369
-
Tidskriftsartikel (refereegranskat)abstract
- Severe congenital neutropenia (SCN) is characterized by low blood neutrophil counts, early bacterial infections, and risk of leukaemia development. As yet, no population-based incidence estimates of SCN have been reported. Children less than 16years of age with SCN were sought in Sweden during the 20-year period 1987-2006 by a questionnaire to all Swedish Departments of Paediatrics and by reviewing the Swedish Health and Welfare Statistical Databases. Thirty-two patients were diagnosed with congenital neutropenia during this period. All received treatment with recombinant granulocyte-colony stimulating factor (G-CSF). Twenty-one patients were diagnosed as SCN or probable SCN, corresponding to 1·0 per 100000 live births. Nine (43%) had ELANE mutations, four (19%) HAX1 mutations and eight (38%) were children with disease of unknown genetic aetiology. Four out of 21 patients (19%) developed myelodysplastic syndrome/leukaemia and three (14%) died, all with leukaemia. The cumulative incidence of myelodysplastic syndrome/leukaemia was 31%. The observed incidence of SCN in this population-based study was higher than previously estimated, possibly because genetic testing now can identify SCN cases previously thought to be idiopathic or benign neutropenia. The risk of developing myelodysplastic syndrome/leukaemia is considerable. ELANE mutations are the most commonly identified genetic defects.
|
|
| 12. |
- Carlsson, Göran, 1951, et al.
(författare)
-
Pretherapeutic uracil and dihydrouracil levels in saliva of colorectal cancer patients are associated with toxicity during adjuvant 5-fluorouracil-based chemotherapy.
- 2014
-
Ingår i: Cancer chemotherapy and pharmacology. - : Springer Science and Business Media LLC. - 1432-0843 .- 0344-5704. ; 74:4, s. 757-63
-
Tidskriftsartikel (refereegranskat)abstract
- 5-fluorouracil (5-FU) competes with uracil (Ura) as a substrate for dihydropyrimidine dehydrogenase (DPD). Low DPD activity impairs breakdown of Ura to dihydrouracil (UH2) and is associated with toxicity during 5-FU-based chemotherapy. Calculation of the 5-FU dose is based on body surface area, and new tools are needed to individualize treatment. The aim of study was to measure Ura and UH2 in saliva of patients with colorectal cancer and relate levels to treatment-induced toxicity.
|
|
| 13. |
- Derwinger, Kristoffer, 1969, et al.
(författare)
-
A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer.
- 2011
-
Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 1532-2157. ; 37:7, s. 583-8
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to assess the feasibility of preoperative chemotherapy and possible tumour response using Pemetrexed (Alimta) in rectal cancer.
|
|
| 14. |
- Derwinger, Kristoffer, 1969, et al.
(författare)
-
A study of the MTHFR gene polymorphism C677T in colorectal cancer.
- 2009
-
Ingår i: Clinical colorectal cancer. - 1533-0028. ; 8:1, s. 43-8
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to examine the clinical significance of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T in colorectal cancer (CRC). The hypothesis was that the genotype could affect the risk of cancer development and the results of cancer treatment. PATIENTS AND METHODS: Genotyping was made for a random 30% (n = 544) of all patients treated for CRC at our unit from 1999 to 2006 (n = 1812). Basic clinical and pathologic factors were analyzed by genotype group and also compared with those of the entire cohort. Tolerability of chemotherapy and possible side effects were analyzed by genotype. Survival was analyzed by genotype for all stages for patients treated between 1999 and 2003. The genotype prevalence was also compared with a control material of healthy blood donors. RESULTS: No genotype was associated with an increased risk of CRC or higher cancer stage. The patients with CT/TT genotype had significantly greater risk of suffering side effects from fluoropyrimidine (5-fluorouracil) treatment (P < .05). In stage III colon cancer, the patients with CT/TT genotype had a poorer prognosis than those with the CC genotype. The difference was significant in univariate (P < .003) and multivariate (P < .040) analysis. Though the genotype-associated side effect risks remained in stage IV, the effect on survival was not significant (P < .1). CONCLUSION: The MTHFR polymorphism C677T does, in our material, not affect the risk of CRC; however, it can affect the sensitivity to chemotherapy and the risk of side-effects and therefore survival in stage III and possibly stage IV colon cancer. It could be a future predictive factor in the choice of a treatment regimen.
|
|
| 15. |
- Derwinger, Kristoffer, 1969, et al.
(författare)
-
Defining stage III disease in colorectal cancer--aspects on treatment and evaluation of survival.
- 2010
-
Ingår i: Journal of surgical oncology. - : Wiley. - 1096-9098 .- 0022-4790. ; 102:5, s. 424-7
-
Tidskriftsartikel (refereegranskat)abstract
- Stage III in colorectal cancer is defined by presence of node metastasis, whereas distant growth constitutes stage IV. The aim was to describe prognosis in high risk groups of stage III in relation to survival in stage IV, along with possible effect on research and treatment.
|
|
| 16. |
|
|
| 17. |
- Derwinger, Kristoffer, 1969, et al.
(författare)
-
Stage migration in colorectal cancer related to improved lymph node assessment
- 2007
-
Ingår i: Eur J Surg Oncol. - 0748-7983. ; 33:7, s. 849-53
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of the study was to evaluate the clinical impact of improved cooperation between the treating surgeons and pathologists in a high volume surgical unit. As a measure we used the staging process with special focus on lymph node assessment. FINDINGS: Comparing two periods 5years apart, we found a significant increase in the number of nodes examined and also an increase in the number of metastasis-positive nodes. Concurrently, we observed a trend in stage migration from stage I/II towards stage III, whilst stage IV remained unchanged. This was one factor that contributed to an increase in the number of patients treated with adjuvant chemotherapy. We also found that the number of assessed nodes had an impact on survival in stage II. The major change in practise was the implementation of a multidisciplinary team conference and the associated possibility of reciprocal feedback. CONCLUSION: Lymph node status has a key role in cancer staging and in the selection of further therapy. The quality and the standard of the assessment can be improved through multidisciplinary cooperation and it has an impact on the clinical decisions and can affect long-term survival. A correct node status should be mandatory in the evaluation of prognostic factors.
|
|
| 18. |
- Emland, Frans, et al.
(författare)
-
Prolonged postoperative length of stay may be a valuable marker for susceptibility to relapse beyond established risk factors in patients with stage III colon cancer
- 2022
-
Ingår i: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Delay from surgery to adjuvant chemotherapy causes impaired survival among patients undergoing radical resection for stage III colon cancer, and the underlying mechanism for this is incompletely clarified. It is established that prolonged postoperative hospital length of stay (LOS) is associated with delayed initiation of the adjuvant treatment driving the assumption that prolonged LOS is prognostically unfavorable due to this fact and case mix factors. We hypothesize that prolonged LOS after surgery is a valuable marker for susceptibility to relapse that is not detected in established prognostic factors and, alone, associated with a shorter disease-free survival (DFS). Materials and methods: A total of 690 consecutive patients undergoing elective radical resection for stage III colon cancer in 2000–2015 were identified in a prospective detailed facility database. Univariate and multivariate analyses were performed using Cox proportional hazards model in the evaluation of LOS as an independent prognostic factor. Results: Short postoperative LOS, low comorbidity, and few complications were associated with longer DFS (p < 0.01). Fewer patients in the short and intermediate LOS groups had a relapse in their disease (28% and 33%, respectively), compared to the patients with longer LOS (40%, p < 0.05). LOS was a prognostic factor for DFS in the unadjusted univariate model (HR 1.04 per unit change) and remained statistically significant in the adjusted multivariate analysis, with a HR of 1.03 per hospital day (p < 0.01). Conclusions: Postoperative LOS independently correlates with the risk of recurrence and DFS, regardless of if adjuvant chemotherapy is given, along with the factors such as age, comorbidity, complications, and tumor features. We propose a further investigation into the causal mechanisms based on tumor and host biology linking LOS to DFS beyond established risk factors.
|
|
| 19. |
- Gustavsson, Bengt, 1947, et al.
(författare)
-
A Review of the Evolution of Systemic Chemotherapy in the Management of Colorectal Cancer.
- 2015
-
Ingår i: Clinical colorectal cancer. - : Elsevier BV. - 1938-0674 .- 1533-0028. ; 14:1, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Herein we present a historical review of the development of systemic chemotherapy for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in 1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and the advent of novel cytotoxic agents, including the topoisomerase I inhibitor irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin) and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in overall survival times of approximately 2 years. When used as adjuvant therapy, FOLFOX also improves survival and is now the gold standard of care in this setting. Biological agents have been discovered that enhance the effect of cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that targets vascular endothelial growth factor, a central regulator of angiogenesis) and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal growth factor receptor). Despite the ongoing development of novel antitumor agents and therapeutic principles as we enter the era of personalized cancer medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to be the cornerstone of treatment for patients with CRC.
|
|
| 20. |
- Gustavsson, Bengt, 1947, et al.
(författare)
-
Molecular determinants of efficacy for 5-FU-based treatments in advanced colorectal cancer: mRNA expression for 18 chemotherapy-related genes.
- 2009
-
Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 124:5, s. 1220-6
-
Tidskriftsartikel (refereegranskat)abstract
- 5-Fluorouracil (5-FU)-based regimens remain a cornerstone in the treatment of colorectal cancer (CRC). However, the attendant toxicity prevents these regimens from reaching maximum therapeutic potential. In this retrospective analysis, we examined the pretreatment expression of 18 genes in archival tumor bank samples from patients with advanced CRC to determine if one or more of the selected genes showed promise as either a prognostic or predictive marker of 5-FU-based treatment outcomes. One hundred and forty-four CRC patient samples (collected from 1983 to 2004) were analyzed via real-time PCR for gene expression. Univariate analyses were used to correlate gene expression with efficacy and time-to-event variables. Low thymidine phosphorylase (TP), dihydrofolate reductase, dihydropyrimidine dehydrogenase (DPD), excision repair cross-complementing 1 (ERCC1) and thymidylate synthase gene expression were associated with better time-to-progression in the entire population. Low TP, DPD and ERCC1 expression were independently associated with improved overall survival. Low TP gene expression was also predictive of response. This study suggests that TP gene expression in particular is a predictive as well as a prognostic biomarker for advanced CRC patients. Gene panels assessing pretreatment TP, DPD, ERCC1, dihydrofolate reductase and thymidylate synthase gene expression may help improve the therapeutic potential of 5-FU- or other novel antifolate-based regimens. Further analysis of the prognostic or predictive value of these genes in prospective trials in CRC patients seems warranted.
|
|
