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1.
  • Hogberg, T, et al. (författare)
  • A prospective population-based management program including primary surgery and postoperative risk assessment by means of DNA ploidy and histopathology. Adjuvant radiotherapy is not necessary for the majority of patients with FIGO stage I-II endometrial cancer
  • 2004
  • Ingår i: International Journal of Gynecological Cancer. - : Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 14:3, s. 437-450
  • Tidskriftsartikel (refereegranskat)abstract
    • A management program for FIGO stage I-II nonserous, nonclear-cell adenocarcinomas was evaluated. Histopathology and DNA ploidy were used to estimate postoperatively the risk of progression or death of disease and to tailor treatment. The patient material was a population-based consecutive cohort of all women with endometrial cancer in the Southern Swedish Health Care Region diagnosed between June 1993 and June 1996 (n = 553). Of these, 335 were eligible for the management program. Patients estimated to be at low risk were treated by surgery only, while high-risk patients also received vaginal brachytherapy. A large low-risk group consisting of 84% (n = 283) of the patients with an estimated disease-specific 5-year survival of 96% (95% CI = 93-98%) was identified. The high-risk group (n = 52, 16%) showed a worse outcome with an 80% 5-year disease-specific survival (95% CI = 65-89%). The difference in survival between the groups was highly significant (P < 0.0001). Half of the progressions were distant in the high-risk group. Although there is a clear indication for adjuvant therapy for this group, locoregional radiotherapy could be expected to fail in cases with distant progression. Thus, effective systemic treatments need to be developed. Low-risk patients, constituting the majority (84%) of the patients, can be safely treated by surgery only.
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2.
  • Koul, Anjila, et al. (författare)
  • TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - : Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 12:4, s. 362-371
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (>= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P < 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy.
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3.
  • Kristensen, GB, et al. (författare)
  • First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin
  • 2003
  • Ingår i: International Journal of Gynecological Cancer. - : Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 13, s. 172-177
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma.. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m(2), 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis &GE; grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P=0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.
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4.
  • Sorbe, Bengt, et al. (författare)
  • Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up
  • 2008
  • Ingår i: International Journal of Gynecological Cancer. - : Blackwell Publishing Ltd. - 1048-891X .- 1525-1438. ; 18:4, s. 803-808
  • Tidskriftsartikel (refereegranskat)abstract
    • There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.
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5.
  • Bergmark, K., et al. (författare)
  • Lymphedema and bladder-emptying difficulties after radical hysterectomy for early cervical cancer and among population controls
  • 2006
  • Ingår i: Int J Gynecol Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 16:3, s. 1130-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to acquire knowledge that can be used to refine radical hysterectomy to improve quality-of-life outcome. Data were collected in 1996-1997 by means of an anonymous postal questionnaire in a follow-up study of two cohorts (patients and population controls). We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-1992 at the seven departments of gynecological oncology in Sweden and 489 population controls. Ninety three (37%) of the 256 women with a history of cervical cancer who answered the questionnaire (77%) were treated with surgery alone. Three-hundred fifty population controls answered the questionnaire (72%). Women treated with radical hysterectomy, as compared with controls, had an 8-fold increase in symptoms indicating lymphedema (25% reported distress due to lymphedema), a nearly 9-fold increase in difficult emptying of the bladder, and a 22-fold increase in the need to strain to initiate bladder evacuation. Ninety percent of the patients were not willing to trade off survival for freedom from symptoms. Avoiding to induce long-term lymphedema or bladder-emptying difficulties would probably improve quality of life after radical hysterectomy (to cure cervical cancer). Few women want to compromise survival to avoid long-term symptoms.
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6.
  • Graflund, M., et al. (författare)
  • HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas
  • 2014
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 14:5, s. 896-902
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.
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7.
  • Graflund, Marianne, et al. (författare)
  • Immunohistochemical expression of p53, bcl-2, and p21(WAF1/CIP1) in early cervical carcinoma : correlation with clinical outcome
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to assess the value of p53, bcl-2, and p21(WAF1/CIP1) immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21(WAF1/CIP1). None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21(WAF1/CIP1) appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
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8.
  • Graflund, Marianne, et al. (författare)
  • Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
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9.
  • Graflund, Marianne, et al. (författare)
  • The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:2, s. 149-157
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.
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10.
  • Graflund, Marianne, et al. (författare)
  • The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix
  • 2002
  • Ingår i: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 12:1, s. 32-41
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I-II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965-1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.
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