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  • Cashin, Peter H., et al. (författare)
  • Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases : A randomised trial
  • 2016
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 53, s. 155-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).
  • Cashin, Peter H, et al. (författare)
  • Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis a case-control study
  • 2012
  • Ingår i: Annals of Oncology. - Oxford University Press. - 0923-7534 .- 1569-8041. ; 23:3, s. 647-652
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.PATIENTS AND METHODS: A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.RESULTS: Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.CONCLUSION:HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.
  • Cashin, Peter H, 1984-, et al. (författare)
  • Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
  • 2012
  • Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 256:6, s. 1078-1083
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.
  • Cashin, Peter H., et al. (författare)
  • Peritoneal mesothelioma in Sweden A population-based study
  • 2019
  • Ingår i: Cancer Medicine. - 2045-7634 .- 2045-7634. ; 8:14, s. 6468-6475
  • Tidskriftsartikel (refereegranskat)abstract
    • The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.
  • Cashin, Peter, 1984-, et al. (författare)
  • Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases
  • 2018
  • Ingår i: European Journal of Surgical Oncology. - ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 44:7, s. 983-990
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.
  • Collin, Åsa, et al. (författare)
  • The effect of local gentamicin-collagen on perineal wound complications and cancer recurrence after abdominoperineal resection : a multicentre randomised controlled trial
  • 2013
  • Ingår i: Colorectal Disease. - 1462-8910 .- 1463-1318. ; 15:3, s. 341-346
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:  Perineal wound sepsis is a common problem after abdominoperineal resection of the rectum (APR), with an reported incidence of 10-15% in previously non-radiated patients, 20-30% in patients given preoperative radiation, and 50% among patients submitted to preoperative radiation combined with chemotherapy. The local application of gentamicin-collagen was evaluated to determine whether its use in the perineal wound reduced the risk complications and had an effect on cancer recurrence.Method: In this prospective multicentre (7 hospitals) randomised controlled trial, 102 patients undergoing APR due to cancer or benign disease were randomised into two groups including surgery with gentamicin-collagen (GS+ n=52), or surgery without gentamicin-collagen (GS- n=50), Patients were followed at 7, 30 and 90 days and at one and five years.Results:  There were no statistically significant differences between the two groups regarding perineal wound complications, infectious or non-infectious or cancer recurrence.Conclusion: There was no statistically significant effect on perineal wound complications or cancer recurrence following the local administration of gentamicin-collagen during APR.
  • Danielson, Johan, 1975-, et al. (författare)
  • Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
  • 2013
  • Ingår i: Techniques in Coloproctology. - 1123-6337 .- 1128-045X. ; 17:4, s. 389-395
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Stabilized non-animal hyaluronic acid/dextranomer (NASHA® Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.METHODS:Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.RESULTS: Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.CONCLUSIONS:Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.
  • Danielson, Johan, 1975-, et al. (författare)
  • Injectable bulking treatment of persistent faecal incontinence after anorectal malformations. A preliminary report.
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • Background/PurposeDuring the last decades injectable bulking therapy has emerged as a promising treatment option for fecal incontinence (FI). Very little has been published on the use of injectable bulking therapy on patients with persistent FI after anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.MethodsSeven adult patients with persistent FI after ARM were treated with perianal submucuos injection of NASHA/Dx. They were evaluated preoperatively and at three and six months after treatment with a validated bowel function questionnaire and a two-week bowel diary as well as FIQL and SF-36 quality of life questionnaires.ResultsBefore treatment mean Miller incontinence score was 13,7 and the mean number of incontinence episodes over two weeks was 20,7. At 6 months after treatment the corresponding figures were 10,7 (P=0,1088) and 5,3 (P=0,0180) respectively. No significant changes could be found in either FIQL or SF-36 scores. No serious adverse events occurred during the study.ConclusionsNASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Long-term follow up of larger patient series as well as studies on patients in adolescence are needed. 
  • Danielson, Johan, 1975-, et al. (författare)
  • Injectable bulking treatment of persistent fecal incontinence in adult patients after anorectal malformations
  • 2020
  • Ingår i: Journal of Pediatric Surgery. - W B SAUNDERS CO-ELSEVIER INC. - 0022-3468 .- 1531-5037. ; 55:3, s. 397-402
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Purpose: Injectable bulking therapy has emerged as a treatment for fecal incontinence (IT, however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic add with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.Methods: Seven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FTQL and SF-36 quality of life questionnaires.Results: Before treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8-52). At 6 months, the corresponding figures were 53 (median 4, range 0-19, p = 0.018), and at 18 months the figures were 4.3 (median 2, range 1-20,p = 0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6 months was noted (p = 0.04). No serious adverse events occurred.Conclusions: NASHA/Dx is a promising treatment option for selected adult patients with persistent Ft after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed. 
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