| 1. |
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| 2. |
- Blom, Johannes, et al.
(author)
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A 9-year follow-up study of participants and nonparticipants in sigmoidoscopy screening : importance of self-selection
- 2008
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 17:5, s. 1163-1168
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Journal article (peer-reviewed)abstract
- BACKGROUND: Self-selection may compromise cost-effectiveness of screening programs. We hypothesized that nonparticipants have generally higher morbidity and mortality than participants. METHODS: A Swedish population-based random sample of 1,986 subjects ages 59 to 61 years was invited to sigmoidoscopy screening and followed up for 9 years by means of multiple record linkages to health and population registers. Gender-adjusted cancer incidence rate ratio (IRR) and overall and disease group-specific and mortality rate ratio (MRR) with 95% confidence intervals (95% CI) were estimated for nonparticipants relative to participants. Cancer and mortality rates were also estimated relative to the age-matched, gender-matched, and calendar period-matched Swedish population using standardized incidence ratios and standardized mortality ratios. RESULTS: Thirty-nine percent participated. The incidence of colorectal cancer (IRR, 2.2; 95% CI, 0.8-5.9), other gastrointestinal cancer (IRR, 2.7; 95% CI, 0.6-12.8), lung cancer (IRR, 2.2; 95% CI, 0.8-5.9), and smoking-related cancer overall (IRR, 1.4; 95% CI, 0.7-2.5) tended to be increased among nonparticipants relative to participants. Standardized incidence ratios for most of the studied cancers tended to be >1.0 among nonparticipants and <1.0 among participants. Mortality from all causes (MRR, 2.4; 95% CI, 1.7-3.4), neoplastic diseases (MRR, 1.9; 95% CI, 1.1-3.5), gastrointestinal cancer (MRR, 4.7; 95% CI, 1.1-20.7), and circulatory diseases (MRR, 2.3; 95% CI, 1.2-4.2) was significantly higher among nonparticipants than among participants. Standardized mortality ratio for the studied outcomes tended to be increased among nonparticipants and was generally decreased among participants. CONCLUSION: Individuals who might benefit most from screening are overrepresented among nonparticipants. This self-selection may attenuate the cost-effectiveness of screening programs on a population level.
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| 3. |
- Laurell, Helena, 1965-
(author)
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Acute Abdominal Pain
- 2006
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Doctoral thesis (other academic/artistic)abstract
- The aim was to identify diagnostic difficulties for acute abdominal pain at the emergency department and during hospital stay. A total of 3349 patients admitted to Mora Hospital with acute abdominal pain of up to seven days duration, were registered prospectively for history and clinical signs according to a structured schedule. The preliminary diagnosis from the attending physician at the emergency department, any investigations or surgery and final diagnosis were registered at a follow-up after at least one year. There were no differences in diagnostic performance between physicians with 0.5 to 5 years of medical experience. The information collected and a careful examination of the patient was more important than formal competence. The main differential diagnostic problem was non-specific abdominal pain; this was the same for diagnoses requiring surgery. Patients originally diagnosed as not needing surgery had a median delay before operation of 22 hours (mean 40 hours, with 95% confidence interval of 30-50 hours), compared to 8 hours (mean 15 hours, 95% confidence interval of 12-28 hours) for patients with the same final follow-up diagnosis as the preliminary diagnosis. Constipation was a diagnostic pitfall, as 9% of the patients considered constipated required surgery for potentially life threatening reasons and 8% were later found to have an abdominal malignancy. Both the preliminary diagnosis and the discharge diagnosis were less reliable for elderly patients than for younger patients. Elderly patients often had specific organ disease and arrived at the emergency department after a longer history of abdominal pain. This study confirms that assessment of suspected appendicitis can still be based on clinical judgements combined with laboratory tests. Classical clinical findings indicating localised inflammation, such as isolated pain in the right iliac fossa, rebound tenderness, right-sided rectal tenderness, pain migration to the right iliac fossa, local guarding and aggravation of pain when moving, were reliable for predicting acute appendicitis. A CT scan can be saved for the more equivocal cases of acute abdominal pain. A generous strategy regarding CT scan among elderly patients with acute abdominal pain, even in the absence of pronounced signs of an inflammatory intra-abdominal process, is recommended.
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| 4. |
- Morris, Eva J. A., et al.
(author)
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A population-based comparison of the survival of patients with colorectal cancer in England, Norway and Sweden between 1996 and 2004
- 2011
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 60:8, s. 1087-1093
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Journal article (peer-reviewed)abstract
- Objective To examine differences in the relative survival and excess death rates of patients with colorectal cancer in Norway, Sweden and England. Methods All individuals diagnosed with colorectal cancer (ICD10 (International Classification of Diseases, 10th revision) C18-C20) between 1996 and 2004 in England, Norway and Sweden were included in this population-based study of patients with colorectal cancer. The main outcome measures were 5-year cumulative relative period of survival and excess death rates stratified by age and period of follow-up. Results The survival of English patients with colorectal cancer was significantly lower than was observed in both Norway and Sweden. Five-year age-standardised colon cancer relative survival was 51.1% (95% CI 50.1% to 52.0%) in England compared with 57.9% (95% CI 55.2% to 60.5%) in Norway and 59.9% (95% CI 57.7% to 62.0%) in Sweden. Five-year rectal cancer survival was 52.3% (95% CI 51.1% to 53.5%) in England compared with 60.7% (95% CI 57.0% to 64.2%) and 59.8% (95% CI 56.9% to 62.6%) in Norway and Sweden, respectively. The lower survival for colon cancer in England was primarily due to a high number of excess deaths among older patients in the first 3 months after diagnosis. In patients with rectal cancer, excess deaths remained elevated until 2 years of follow-up. If the lower excess death rate in Norway applied in the English population, then 890 (13.6%) and 654 (16.8%) of the excess deaths in the colon and rectal cancer populations, respectively, could have been prevented at 5 years follow-up. Most of these avoidable deaths occurred shortly after diagnosis. Conclusions There was significant variation in survival between the countries, with the English population experiencing a poorer outcome, primarily due to a relatively higher number of excess deaths in older patients in the short term after diagnosis. It seems likely, therefore, that in England a greater proportion of the population present with more rapidly fatal disease (especially in the older age groups) than in Norway or Sweden.
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| 5. |
- Møller, Henrik, et al.
(author)
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Colorectal cancer survival in socioeconomic groups in England : Variation is mainly in the short term after diagnosis
- 2012
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:1, s. 46-53
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Journal article (peer-reviewed)abstract
- The objective of this study was to examine differences in cancer survival between socioeconomic groups in England, with particular attention to survival in the short term of follow-up. PATIENTS AND METHODS: Individuals diagnosed with colorectal cancer between 1996 and 2004 in England were identified from cancer registry records. Five-year cumulative relative survival and excess death rates were computed. RESULTS: For colon cancer there was a very high excess death rate in the first month of follow-up, and the excess death rate was highest in the socioeconomically deprived groups. In subsequent periods, excess mortality rates were much lower and there was less socioeconomic variation. The pattern of variation in excess death rates was generally similar in rectal cancer but the socioeconomic difference in death rates persisted several years longer. If the excess death rates in the entire colorectal cancer patient population were the same as those observed in the most affluent socioeconomic quintile, the annual reduction would be 360 deaths in colon cancer and 336 deaths in rectal cancer patients. These deaths occurred almost entirely in the first month and the first year after diagnosis. CONCLUSION: Recent developments in the national cancer control agenda have included an increasing emphasis on outcome measures, with short-term cancer survival an operational measure of variation and progress in cancer control. In providing clues to the nature of the survival differences between socioeconomic groups, the results presented here give strong support for this strategy.
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| 6. |
- Påhlman, Lars, et al.
(author)
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Antimicrobial activity of fibrinogen and fibrinogen-derived peptides : a novel link between coagulation and innate immunity
- 2013
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 930-939
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Journal article (peer-reviewed)abstract
- Fibrinogen is a key player in the blood coagulation system, and is upon activation with thrombin converted into fibrin that subsequently forms a fibrin clot. In the present study, we investigated the role of fibrinogen in the early innate immune response. Here we show that the viability of fibrinogen-binding bacteria is affected in human plasma activated with thrombin. Moreover, we found that the peptide fragment GHR28 released from the β-chain of fibrinogen has antimicrobial activity against bacteria that bind fibrinogen to their surface, whereas non-binding strains are unaffected. Notably, bacterial killing was detected in Group A Streptococcus bacteria entrapped in a fibrin clot, suggesting that fibrinogen and coagulation is involved in the early innate immune system to quickly wall off and neutralise invading pathogens.
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| 7. |
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| 8. |
- Adam, René, et al.
(author)
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Managing synchronous liver metastases from colorectal cancer : A multidisciplinary international consensus
- 2015
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In: Cancer Treatment Reviews. - : Elsevier BV. - 0305-7372 .- 1532-1967. ; 41:9, s. 729-741
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Journal article (peer-reviewed)abstract
- An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.
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| 9. |
- Agarwal, Shruti, et al.
(author)
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The activation loop tyrosine 823 is essential for the transforming capacity of the c-Kit oncogenic mutant D816V.
- 2015
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In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 34:35, s. 4581-4590
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Journal article (peer-reviewed)abstract
- Oncogenic c-Kit mutations have been shown to display ligand-independent receptor activation and cell proliferation. A substitution of aspartate to valine at amino acid 816 (D816V) is one of the most commonly found oncogenic c-Kit mutations and is found in >90% of cases of mastocytosis and less commonly in germ-cell tumors, core-binding factor acute myeloid leukemia and mucosal melanomas. The mechanisms by which this mutation leads to constitutive activation and transformation are not fully understood. Previous studies have shown that the D816V mutation causes a structural change in the activation loop (A-loop), resulting in weaker binding of the A-loop to the juxtamembrane domain. In this paper, we have investigated the role of Y823, the only tyrosine residue in the A-loop, and its role in oncogenic transformation by c-Kit/D816V by introducing the Y823F mutation. Although dispensable for the kinase activity of c-Kit/D816V, the presence of Y823 was crucial for cell proliferation and survival. Furthermore, mutation of Y823 selectively downregulates the Ras/Erk and Akt pathways as well as the phosphorylation of STAT5 and reduces the transforming capacity of the D816V/c-Kit in vitro. We further show that mice injected with cells expressing c-Kit/D816V/Y823F display significantly reduced tumor size as well as tumor weight compared with controls. Finally, microarray analysis, comparing Y823F/D816V cells with cells expressing c-Kit/D816V, demonstrate that mutation of Y823 causes upregulation of proapoptotic genes, whereas genes of survival pathways are downregulated. Thus, phosphorylation of Y823 is not necessary for kinase activation, but essential for the transforming ability of the c-Kit/D816V mutant.Oncogene advance online publication, 1 December 2014; doi:10.1038/onc.2014.383.
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| 10. |
- Alam, Muhammad Wasi, et al.
(author)
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HIF2α contributes to antiestrogen resistance via positive bilateral crosstalk with EGFR in breast cancer cells.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:10, s. 50-11238
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Journal article (peer-reviewed)abstract
- The majority of breast cancers express estrogen receptor α (ERα), and most patients with ERα-positive breast cancer benefit from antiestrogen therapy. The ERα-modulator tamoxifen and ERα-downregulator fulvestrant are commonly employed antiestrogens. Antiestrogen resistance remains a clinical challenge, with few effective treatments available for patients with antiestrogen-resistant breast cancer. Hypoxia, which is intrinsic to most tumors, promotes aggressive disease, with the hypoxia-inducible transcription factors HIF1 and HIF2 regulating cellular responses to hypoxia. Here, we show that the ERα-expressing breast cancer cells MCF-7, CAMA-1, and T47D are less sensitive to antiestrogens when hypoxic. Furthermore, protein and mRNA levels of HIF2α/HIF2A were increased in a panel of antiestrogen-resistant cells, and antiestrogen-exposure further increased HIF2α expression. Ectopic expression of HIF2α in MCF-7 cells significantly decreased sensitivity to antiestrogens, further implicating HIF2α in antiestrogen resistance. EGFR is known to contribute to antiestrogen resistance: we further show that HIF2α drives hypoxic induction of EGFR and that EGFR induces HIF2α expression. Downregulation or inhibition of EGFR led to decreased HIF2α levels. This positive and bilateral HIF2-EGFR regulatory crosstalk promotes antiestrogen resistance and, where intrinsic hypoxic resistance exists, therapy itself may exacerbate the problem. Finally, inhibition of HIFs by FM19G11 restores antiestrogen sensitivity in resistant cells. Targeting HIF2 may be useful for counteracting antiestrogen resistance in the clinic.
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| 11. |
- Aldman, Malin Hagstrand, et al.
(author)
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Endocarditis due to Staphylococcus lugdunensis-a retrospective national registry-based study
- 2021
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In: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 40, s. 1103-1106
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Journal article (peer-reviewed)abstract
- We present characteristics of infective endocarditis (IE) caused by Staphylococcus lugdunensis and compare with IE caused by Staphylococcus aureus and other CoNS, in the National Swedish Registry of IE (2008-2018). Thirty episodes of S. lugdunensis IE were registered, of which 21 cases affected native valves, and 7 patients were subjected to surgery. The mortality rate at 30 days was significantly higher for S. lugdunensis IE (20%, n = 6), than for IE caused by other CoNS (7%) or S. aureus (9%) p = 0.016. Septic embolisation was only reported in two cases (7%). The most common treatment was isoxazolyl penicillin (n = 18).
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| 12. |
- Andréasson, Håkan, et al.
(author)
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Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
- 2013
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 40:8, s. 930-936
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Journal article (peer-reviewed)abstract
- Background: Cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy is a highly invasive treatment of peritoneal metastasis and requires many surgical procedures before mastering. The aim of this study was to estimate how many procedures are needed before stabilization can be seen in surgical outcome (R1 surgery, adverse events and bleeding) in patients with pseudomyxoma peritonei (PMP). Patients and methods: All 128 patients with PMP who were treated with CRS alone or CRS plus perioperative intraperitoneal chemotherapy between 2003 and 2008 at the Uppsala University Hospital, Uppsala, Sweden, were included. The learning curve was calculated using the partial least square (PLS) and cumulative sum control chart (CUSUM) graph. Two groups were formed based on the results of the learning curve. The learning curve plateau was considered the same as the stabilization in the CUSUM graph. Group I consisted of patients included during the learning period (n = 73) and Group 11 of patients treated after the learning period ended (n = 55). Comparisons between the groups were made on surgical outcome, survival and adverse events. Results: Stabilization was seen after 220 +/- 10 procedures. A higher occurrence of R1 surgery was seen in Group H (80%) compared to Group I (48%; P = 0.0002). Overall survival increased at four years after surgery in Group H compared to Group I (80% vs. 63%; P = 0.02). Conclusion: CRS plus perioperative intraperitoneal chemotherapy is a highly demanding procedure that requires more than 200 procedures before optimisation in surgical outcome is seen.
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| 13. |
- Andréasson, Håkan
(author)
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Pseudomyxoma Peritonei : Aspects of Natural History, Learning Curve, Treatment Outcome and Prognostic Factors
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous peritoneal metastasis (PM). Different loco-regional treatment strategies, i.e. debulking surgery and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), have changed the prognosis for these patients. CRS is an aggressive surgical procedure with a long learning curve. PMP exists in different types; how many depends on which classification is used.The aims of this thesis were to investigate the time-frame of PMP development from an isolated appendiceal neoplasm, examine the learning process for CRS, evaluate the differences in treatment outcome between debulking surgery and CRS in combination with HIPEC, to evaluate a more detailed PMP classification and to investigate particularly interesting new cysteine-histidine (PINCH) protein as a prognostic factor for PMP.Retrospectively 26 PMP patients were identified as having had an appendectomy with a neoplasm in the appendix but with no evidence of PM at the appendectomy. They were treated for PMP within a median of 13.1 months (3.8-95.3) after the appendectomy. No difference was seen between the types of PMP regarding the time to a clinically significant development of PMP and how much tumour was found at treatment. CRS is a highly invasive treatment and stabilization in the learning curve was seen after 220±10 procedures. Patients treated with CRS+HIPEC had a better 5-year overall survival (OS) than patients treated with debulking surgery, 74% vs. 40%. CRS increased the rate of complete cytoreduction from 25% in patients treated with debulking surgery to 72%. The new four-grade PMP classification showed very good inter-rater agreement between two independent pathologists and a difference in survival rates was observed between the different grades. A positive PINCH staining was recorded in 83% of the tumours and that was associated with poorer survival.
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| 14. |
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| 15. |
- Andréasson, Sara Näslund, et al.
(author)
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Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles
- 2008
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 35:7, s. 780-784
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Journal article (peer-reviewed)abstract
- BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3cm from the breathing area of the surgeon (personal sampling) and 3m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1mum. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3x10(6)particle/ml/h (pt/ml/h)) than in the control group (4.8x10(5)pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6x10(6) pt/ml/h) than in the control group (3.9x10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.
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| 16. |
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| 17. |
- Augestad, Knut M., et al.
(author)
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International preoperative rectal cancer management : staging, neoadjuvant treatment, and impact of multidisciplinary teams
- 2010
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 34:11, s. 2689-2700
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Journal article (peer-reviewed)abstract
- Background Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. Methods One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. Results One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years’ experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventyfour percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p= 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p= 0.0001), MRI for all RC patients (20% vs. 42%, p= 0.03), and ERUS for all RC patients (43% vs. 21%, p= 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR =5.67, stage II + III RR =2.98), quality of pathology report (RR= 4.85), and sphincter-saving surgery (RR = 3.81). Conclusions There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods.
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| 18. |
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| 19. |
- Birgisson, Helgi, 1967-
(author)
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Cancer of the Colon and Rectum : Population Based Survival Analysis and Study on Adverse Effects of Radiation Therapy for Rectal Cancer
- 2006
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Doctoral thesis (other academic/artistic)abstract
- The Swedish Cancer Register was used to determine the relative survival rate in colon and rectal cancer and to estimate the occurrence of second cancers related to radiation therapy for rectal cancer. The Swedish Hospital Discharge Register and hospital records were used to estimate the rate of late adverse effects due to radiation therapy for rectal cancer. The whole Swedish population was the source of the survival studies. Patients participating in the Uppsala Trial and the Swedish Rectal Cancer Trial on radiation therapy for rectal cancer constituted the subjects of the studies on late adverse effects and second cancers.The main results of the survival analysis revealed a significant improvement in the 5-year relative survival rate for both colon and rectal cancer. During the time period 1960-1999, the survival improved from 39.6% to 57.2% in colon cancer and from 36.1% to 57.6% in rectal cancer.Patients irradiated for rectal cancer, in addition to surgery, were at increased risk for a second cancer compared to those treated by surgery alone. This risk increase was mainly found for cancers developing in organs within or adjacent to the irradiated target (relative risk (RR) 2.04; 95% confidence interval (CI) 1.10–3.79). Furthermore, the most important late adverse effects of radiation therapy seem to be those on the gastrointestinal tract, in the form of small bowel obstruction (RR 1.88; 95%CI 1.10–3.20) and abdominal pain (RR 1.92; 95% CI 1.14–3.23). Overall, the benefit of radiation therapy was greater than its drawbacks, as a large reduction in local recurrences and better survival was noted in patients treated preoperatively with irradiation for rectal cancer.In conclusion, significant improvements in the survival of patients with colon and rectal cancers have occurred in the last decades, especially in patients with rectal cancer. These improvements probably are related to advances in surgical and adjuvant treatment. The radiation therapy has several drawbacks, however, including an increased risk of second cancers and of bowel obstruction. This emphasises the need to further improve the radiation technique and to select only those patients for radiation therapy who are most likely to benefit from it.
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| 20. |
- Birgisson, Helgi, et al.
(author)
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Late adverse effects of radiation therapy for rectal cancer : a systematic overview
- 2007
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:4, s. 504-516
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Journal article (peer-reviewed)abstract
- PURPOSE: The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. METHODS: Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5 x 5 Gy radiation therapy with surgery alone. RESULTS: The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. CONCLUSIONS: These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.
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| 21. |
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| 22. |
- Birgisson, Helgi, et al.
(author)
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Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer
- 2015
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 15
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Journal article (peer-reviewed)abstract
- Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.
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| 23. |
- Birgisson, Helgi, et al.
(author)
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The correlation between a family history of colorectal cancer and survival of patients with colorectal cancer
- 2009
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In: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 8:4, s. 555-561
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Journal article (peer-reviewed)abstract
- The purpose was to analyze survival of patients with colorectal cancer and a positive family history for colorectal cancer in first degree relatives compared with those with no such family history and to determine whether differences in survival could be explained by known clinico-pathological factors. During 2000-2003, 318 consecutive patients with colorectal cancer answered a written questionnaire about their family history for colorectal cancer. During a 6-year follow-up, recurrences and survival were registered. Thirty-one (10%) patients had a first-degree relative with colorectal cancer, moreover two patients fulfilled the criteria of hereditary non-polyposis colorectal cancer and were excluded. Patients with a first-degree relative with colorectal cancer had better survival and lower risk for recurrences compared to those with no relatives with colorectal cancer. In a multivariate analysis including age, gender, stage of disease, tumor differentiation, vascular invasion and family history, patients with first-degree relatives with colorectal cancer had lower risks for death (RR 0.37; 95% CI 0.17-0.78) and death from cancer (RR 0.25; 95% CI 0.08-0.80), compared to those with a no relative with colorectal cancer. The differences were seen in patients with colon cancer but not rectal cancer. Family history for colorectal cancer in a first-degree relative is an individual prognostic factor in patients with colon cancer and could not be explained by known clinico-pathological factors. The value of family history taking in patients with colon cancer is therefore not only to identify families with hereditary colorectal cancer, but also to add information to the prognosis of the patients.
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| 25. |
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