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Sökning: WFRF:(Smedh K)

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  • Nilsson, K., et al. (författare)
  • Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial
  • 2023
  • Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:11, s. 1015-1024
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer.Patients and methods: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type.Results: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107).Conclusion: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.
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  • Andersson, Peter, et al. (författare)
  • Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments
  • 1998
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 33:4, s. 423-429
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.
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  • Asplund, Dan, et al. (författare)
  • Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence
  • 2017
  • Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 32:11, s. 1639-1647
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Quality of life may predict survival. In addition to clinical variables, it may be influenced by psychological factors, some of which may be accessible for intervention. The primary objective of this study was to investigate the association of intrusive thoughts and the patients' sense of coherence with pretreatment quality of life in patients with newly diagnosed rectal cancer. Methods Patients were prospectively included in 16 hospitals in Sweden and Denmark. They answered an extensive questionnaire after receiving their treatment plan. Clinical data were retrieved from national quality registries for rectal cancer. Results Of 1248 included patients, a total of 1085 were evaluable. Pretreatment global health-related and overall quality of life was lower in patients planned for palliative compared with curative treatment (median 53 vs. 80 on the EuroQoL visual analogue scale, p < 0.001 and odds ratio 0.56, 95% confidence interval 0.36-0.88, respectively). Quality of life was associated with intrusive thoughts (odds ratio 0.33, 95% confidence interval 0.24-0.45) and sense of coherence (odds ratio 0.44, 95% confidence interval 0.370.52) irrespective of the treatment plan. Conclusions Pretreatment quality of life was influenced by the intent of treatment as well as by intrusive thoughts and the patients' sense of coherence. Interventions could modify these psychological factors, and future studies should focus on initiatives to improve quality of life for this group of patients.
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  • Isacson, Daniel, et al. (författare)
  • Outpatient, non-antibiotic management in acute uncomplicated diverticulitis : a prospective study
  • 2015
  • Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 30:9, s. 1229-1234
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate outpatient, non-antibiotic management in acute uncomplicated diverticulitis with regard to admissions, complications, and recurrences, within a 3-month follow-up period. A prospective, observational study in which patients with computer tomography-verified acute uncomplicated diverticulitis were managed as outpatients without antibiotics. The patients kept a personal journal, were contacted daily by a nurse, and then followed up by a surgeon at 1 week and 3 months. In total, 155 patients were included, of which 54 were men; the mean age of the patients was 57.4 years. At the time of diagnosis, the mean C-reactive protein and white blood cell count were 73 mg/l and 10.5 x 10(9), respectively, and normalized in the vast majority of patients within the first week. The majority of the patients (97.4 %) were managed successfully as outpatients without antibiotics, admissions, or complications. In only four (2.6 %) patients, the management failed because of complications in three and deterioration in one. These patients were all treated successfully as inpatients without surgery. Five patients had recurrences and were treated as outpatients without antibiotics. Follow-up colonic investigations revealed cancer in two patients and polyps in 13 patients. Previous results of low complication rates with the non-antibiotic policy were confirmed. The new policy of outpatient management without antibiotics in acute uncomplicated diverticulitis is now shown to be feasible, well functioning, and safe.
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  • Smedh, K, et al. (författare)
  • Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.
  • 1999
  • Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 45:4, s. 464-70
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.
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  • Smedh, Ulrika, 1966, et al. (författare)
  • Fourth ventricular thyrotropin induces satiety and increases body temperature in rats
  • 2018
  • Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 314:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Besides its wellknown action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 μg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 μg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection (P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function. © 2018 American Physiological Society. All rights reserved.
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  • Stacey, Simon N, et al. (författare)
  • A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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  • Tackstrom, S., et al. (författare)
  • Use of prophylactic stoma mesh is a risk factor for developing rectus abdominis muscle atrophy
  • 2022
  • Ingår i: Hernia. - : Springer Nature. - 1265-4906 .- 1248-9204. ; 26:2, s. 517-523
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The aim of this study was to evaluate the possible risk factors for developing a parastomal hernia (PSH) in a cohort of rectal cancer patients with and without the application of a retro-muscular prophylactic mesh. The evaluated risk factors included the position of the stoma in the rectus abdominis muscle (RAM), RAM atrophy and shift of abdominal wall midline structures. Methods Rectal cancer patients treated with an abdominoperineal excision or Hartmann's procedure between 2002 and 2015 at Vastmanland Hospital, Sweden was included. Postoperative CT examinations were retrospectively reviewed regarding the presence of PSH and RAM atrophy and for measurements such as position of the stoma in the RAM. Results 116 patients were included, with a median age of 71 years. 70 patients received a prophylactic stoma mesh. 55 patients (47%) had a parastomal hernia at three-year follow-up. Rectus abdominis muscle atrophy was significantly higher in the mesh group compared with the non-mesh group (37% vs 2%; P = 0.04). RAM atrophy was a significant independent protective factor for developing a PSH (P = 0.007; OR 0.15; 95% CI 0.03-0.55). Conclusion Placement of a prophylactic retro-muscular stoma mesh resulted in a high frequency of RAM atrophy distal to the stomal aperture and patients with such atrophy had a lower risk of developing a PSH.
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  • von Holst, S, et al. (författare)
  • Association studies on 11 published colorectal cancer risk loci
  • 2010
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 103:4, s. 575-580
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.
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  • Walming, Sofie, et al. (författare)
  • Quality of life in patients with resectable rectal cancer during the first 24 months following diagnosis
  • 2020
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 22:12, s. 2028-2037
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim An increasing number of patients survive rectal cancer, resulting in more patients living with the side-effects of the treatment. Exploring quality of life before and after treatment enables follow-up and additional treatment to be adjusted to the patient's needs. The aim of the study was to describe the quality of life during the 24 months following diagnosis and to identify risk factors for poor quality of life. Method This is a prospective cohort study of patients with rectal cancer followed up by extensive questionnaires. Patients from 16 surgical departments in Denmark and Sweden from 2012 to 2015 were included. The self-assessed quality of life was measured with a seven-point Likert scale. Results A total of 1110 patients treated with curative intent were included, and the response rate at the 24-month follow-up was 71%. Patients with rectal cancer assessed their quality of life before start of treatment as poorer than that of a reference population. At the 12- and 24-month follow-up, the quality of life on group level had recovered to the same level as for the reference population. Risk factors for poor quality of life included bother with urinary, bowel and stoma function. A reference population was used for comparison. Conclusion The quality of life of patients with resectable rectal cancer recovered to levels comparable to a reference population 12 and 24 months after diagnosis. Our results indicate that the urinary, bowel and stoma function has an impact on quality of life.
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