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Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 109 records · Page 6Linked to original sources
PubMed1999

Improved survival and reduction in local failure rates after preoperative radiotherapy: evidence for the generalizability of the results of Swedish Rectal Cancer Trial.

OBJECTIVE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short-term regimen of high-dose preoperative radiotherapy (5 x 5 Gy) not only reduced the local recurrence rates but also improved the overall survival rate. This compelling evidence will have a significant impact on the primary treatment of rectal cancer. The authors' aim was to explore the representativeness of the study. SUMMARY BACKGROUND DATA: Until the SRCT was presented in 1997, no major trial had established that radiotherapy has a positive effect on the overall survival rate. METHODS: A review of all rectal cancer cases reported to the Swedish Cancer Registry during the same period that the SRCT accrued patients (1987 to 1990) was performed at 57 of 68 participating hospitals. At these 57 hospitals, there were 2366 patients with invasive rectal cancer, with 1664 of these patients fulfilling the criteria for inclusion in the SRCT. RESULTS: Fifty-two percent (866/1664) of eligible patients were included in the SRCT. The patients not included, of whom 8% (67/798) received adjuvant radiotherapy, had an overall 5-year survival rate of 48%, which was identical to the overall survival rate in the SRCT surgery-alone group (48%) but was inferior to the SRCT radiotherapy group (58%). The cancer-specific 5-year survival rates were 65% and 66% among the patients not included and the surgery-alone group, respectively. The local recurrence rates reached 27% in both groups. The results were still comparable when stratifying for curative surgery, tumor stage, and surgical procedure. CONCLUSIONS: The achieved inclusion level of 52% in a randomized multicenter trial is comparatively high. Because the population in the SRCT was representative, it was concluded that the study results are reliable.

Adult↗
PubMed1999

Prognostic value of p53 genetic changes in colorectal cancer.

PURPOSE: To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND METHODS: The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments. RESULTS: Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival. CONCLUSION: Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression.

Aged↗
PubMed1999

A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group.

In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. After adjustment for prognostic factors such as performance status, the difference in survival favoring irinotecan remained highly significant (P = .001). The benefit of irinotecan was also observed through significantly longer survival without performance status deterioration, longer survival without more than 5% weight loss, and longer duration of pain-free survival. Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer.

Antimetabolites, Antineoplastic↗
PubMed1999

Colorectal cancer with and without microsatellite instability involves different genes.

There is evidence supporting a multistep genetic model for colorectal tumorigenesis. In familial adenomatosis polyposis (FAP), the inherited defect is a mutation in the APC gene. The vast majority of all sporadic colorectal cancers also show mutations in the APC gene, and the tumorigenesis in sporadic colorectal cancer and FAP is assumed to involve the same genes. Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germline mutations in DNA mismatch repair genes and, as a result of defective mismatch repair, microsatellite instability (MSI) is frequently seen. Tumorigenesis in HNPCC was first thought to involve mutations in the same genes as in FAP and sporadic colorectal cancer. Recently, however, an alternative pathway to development of colorectal cancer has been suggested in colorectal tumors with MSI, compared to those tumors without the MSI phenotype. We used a consecutive series of 191 sporadic colorectal cancers to find out if there were any differences between the two groups of tumors regarding the prevalence of mutations in the APC, KRAS, TP53, and TGFbetaR2 genes. As expected, 86% (19/22) of MSI-positive tumors showed a mutation in TGFbetaR2, while only one of 164 (0.6%) MSI-negative tumors did. A highly statistically significant negative association was found between MSI and alterations in APC and TP53. The MSI-positive tumors were screened for mutations in exon 3 of beta-catenin, which has been suggested to substitute for the APC mutation in the genesis of colorectal cancer, without finding mutations in any of the 22 MSI-positive tumors. The number of mutations found in KRAS was lower in MSI-positive than in MSI-negative tumors but the difference was not statistically significant. Our results strongly support the idea that carcinogenesis in MSI-positive and MSI-negative colorectal cancer develops through different pathways.

Adenomatous Polyposis Coli↗
PubMed1998

[Sexually transmitted infection as a cause of anal cancer].

Interviews were carried out with 423 women and 93 men with invasive or in situ anal cancer in Denmark and Sweden in a search for clues to the aetiology of this neoplasm. Patients with rectal adenocarcinoma (n = 534) and persons drawn from the background population (n = 554) served as controls. Multivariate logistic regression analyses confirmed previous observations of a strong association between either male homosexual experience or a history of anogenital warts and the risk for anal cancer. Moreover, hitherto unknown, but strong and consistent associations were observed between measures of high heterosexual activity and the risk for anal cancer among both sexes. Polymerase chain reaction analysis revealed human papilloma-virus DNA in the majority (88%) of anal cancer specimens but in none of 20 examined rectal adenocarcinomas. It is concluded that most anal cancers appear to be caused by sexually transmitted types of human papillomaviruses and, consequently, that anal cancer is a potentially preventable neoplasm.

Adenocarcinoma↗
PubMed1998

[Combined radiotherapy and surgery is best against rectal cancer].

The treatment of rectal cancer has changed dramatically during the past twenty years. Adjuvant radiotherapy has been shown to reduce the local recurrence rate by approximately 50 per cent, a reduction associated with a 10-20 per cent improvement in overall survival. Most trials designed to evaluate radiotherapy have not been optimised. Use of the modern mesorectal excision procedure in rectal cancer surgery has reduced the local recurrence rate and improved survival in cases treated with surgery alone. The article consists in a review of advances in our knowledge of radiotherapy and the value of improved surgery, and discussion of radiotherapy used in conjunction with optimised surgical treatment.

Combined Modality Therapy↗
PubMed1998

Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid carcinoma of the anal canal.

PURPOSE: To evaluate the efficacy of induction chemotherapy in combination with radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma. METHODS AND MATERIALS: Thirty-one patients diagnosed during the period 1989-1994 with loco-regionally advanced cancer of the anal canal (phiTmax > or = 4 cm or T4 or N+) were treated with induction chemotherapy consisting of one to three courses of carboplatin (300-375 mg/m2 i.v.) and 5-fluorouracil [5,000 mg/(m2 x 120 h) i.v.] followed by external beam irradiation +/- surgery. RESULTS: The toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor-specific survival, freedom from recurrence, preservation of sphincter, and event-free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%, respectively. CONCLUSION: The results are promising but a well-designed randomized trial is needed to further elucidate the role of induction chemotherapy in the treatment of loco-regionally advanced anal carcinoma.

Adult↗
PubMed1998

Comparative treatment planning between proton and x-ray therapy in esophageal cancer.

PURPOSE: Conformal treatment planning with megavoltage x-rays and protons for five patients with esophageal cancer has been studied in an attempt to determine if there are advantages of using protons instead of x-rays. METHODS AND MATERIALS: For each of the five patients, two different proton plans, one x-ray plan, and one mixed plan with x-rays and protons were made. A three-dimensional treatment planning system, TMS, was used. The evaluation of the different plans was made by applying the tumor control probability (TCP) model proposed by Nahum and Webb and the normal tissue complication (NTCP) model proposed by Lyman on the dose distributions in terms of dose-volume histograms (DVHs). RESULTS: The comparison shows advantages of using protons instead of x-rays for all five patients. The dose-limiting organs at risk are the spinal cord, the lungs, and the heart, but the proton plans also spare the kidneys better than the x-ray plan does. At 5% NTCP in any risk organ, the calculated mean TCP value for the five patients is increased by an average of 20%-units (from 2 to 23%-units) with the best proton plan compared with x-rays only. However, if we assume maximally a 1% risk in the spinal cord and a total NTCP for the two lungs of 100%, the mean TCP value for the five patients is increased from 6 to 49% with the best proton plan compared with x-rays only. The corresponding figure for the mixed plan is 27%. These gains are relatively insensitive to variations within reasonable limits in the biological parameters. CONCLUSIONS: Protons appear to have clear therapeutic advantages over conventional external radiotherapy when treating esophageal carcinoma.

Aged↗
PubMed1998

Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study.

PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose (5 x 5 Gy) radiotherapy reduces local failure rates and improves overall survival. This will have an impact on the primary treatment of rectal cancer. This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection. METHODS: A questionnaire was answered by 92 percent (203/220) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years. Thirty-two patients were excluded, mainly because of postoperative stomas and dementia, which left 171 for analysis. RESULTS: Median bowel frequency per week was 20 in the irradiated group (n = 84) and 10 in the surgery-alone group (n = 87; P < 0.001). Incontinence for loose stools (P < 0.001), urgency (P < 0.001), and emptying difficulties (P < 0.05) were all more common after irradiation. Sensory functions such as "discrimination between gas and stool" and "ability to safely release flatus" did not, however, differ between groups. Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction, compared with 10 percent of the surgery-alone group (P < 0.01). CONCLUSIONS: The study indicates that high-dose radiotherapy influences long-term bowel function, thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques.

Adult↗
PubMed1998

Chemotherapy in the treatment of cancer of the pancreas.

Opinions about the value of chemotherapy in pancreatic cancer vary from the idea that its use should be abandoned because of lack of proven efficacy and considerable toxicity to the idea that it may produce clinically meaningful responses correlated with improved survival. A systematic review of the available literature-based evidence was undertaken. The results are discussed in relation to supportive evidence from recent studies focusing on patient benefit. Six randomized trials of chemotherapy in advanced disease and two in the adjuvant setting with a no-active treatment group were identified. All eight trials were small, and the methodology was not always what is currently desirable. One of four palliative trials reported during the early 1980s, and both trials completed during the 1990s showed a slight survival benefit with chemotherapy. In one of the trials, quality of life (QoL) was also more often improved after 5-fluorouracil-based chemotherapy than after best supportive care. Supportive evidence for a slight prolongation of survival and a clinical benefit also comes from trials comparing different drugs. No standard regimen is defined, although one drug, gemcitabine, has been approved in some countries for the treatment of advanced pancreatic cancer. The two randomized adjuvant trials included a very small number of patients, and, although a survival benefit was seen, conclusive evidence supporting the use of adjuvant chemo (radio) therapy is still lacking. Chemotherapy has low activity in advanced pancreatic cancer, but it can improve survival and well-being in some patients.

Adenocarcinoma↗
PubMed1998

Individual psychological support for cancer patients: utilisation and patient satisfaction.

A short-term, problem-focused Individual Psychological Support (IPS) intervention was evaluated. The IPS was one of the interventions in a study where 527 patients newly diagnosed with breast, colorectal, gastric or prostate cancer were randomised between IPS (n = 265) and a control condition (n = 262). The IPS made use of cognitive-behavioural techniques and aimed at reducing depression and anxiety, to increase the feeling of mastery of the situation and to facilitate active participation in medical treatments. Half of the patients receiving the IPS had more than 2 sessions. After termination of the IPS, the patients were mailed a questionnaire concerning satisfaction with and perceived benefit from the IPS. A majority of the responding patients stated that their problems were addressed to a great extent, that the number of contacts was adequate and that the IPS came at the right time. Patients reporting problems received more sessions and perceived more benefits than patients reporting no problems.

Adult↗
PubMed1998

Bolus injection (2-4 min) versus short-term (10-20 min) infusion of 5-fluorouracil in patients with advanced colorectal cancer: a prospective randomised trial. Nordic Gastrointestinal Tumour Adjuvant Therapy Group.

The use of bolus 5-fluorouracil (5-FU) as a short-term infusion over 10-30 min is increasing at the cost of a push injection, mainly due to practical advantages. Since even a short prolongation of the administration time results in lower 5-FU peak and area under the curve (AUC) levels, there might be a risk of decreased efficacy. The aim of this study was to compare a rapid intravenous (i.v.) 5-FU injection and a short-term 5-FU infusion with respect to objective responses and toxicity in patients with advanced colorectal cancer. 203 patients with measurable advanced colorectal cancer were randomised to bolus 5-FU either as an injection for 2-4 min or as a short-term infusion lasting 10-20 min. In both groups, the 5-FU dose was 500 mg/m2 and leucovorin 60 mg/m2 was given 40 min after the start of 5-FU. Treatment was given on two successive days every other week until progression. Objective tumour regression was seen in 27/100 (27%) in the injection group and in 13/103 (13%) in the infusion group (P = 0.02). Severe toxicity was rare and did not differ significantly between the groups. Progression-free survival tended to be longer in the injection group (P = 0.07), but overall survival did not differ between the groups. Bolus 5-FU should be administered as a rapid i.v. injection rather than as a short-term infusion, since the former rate of administration results in a higher response rate without being significantly more toxic.

Adult↗
PubMed1998

Ki-ras mutations and prognosis in colorectal cancer.

A total of 191 colorectal adenocarcinomas, obtained from consecutive patients with a median follow-up of 6 years, were studied in order to evaluate the possible association of Ki-ras mutations with tumour stage, tumour differentiation and survival time. Resected full-cross tumour samples were screened for Ki-ras mutations in codons 12 and 13 using temporal temperature gradient gel electrophoresis (TTGE). Ki-ras mutations were detected in 62 (32%) of the samples. The most frequent mutation, observed in 21 samples, was from GGT to GAT changing glycine to aspartic acid in codon 12. The study did not show any association between Ki-ras mutations and Dukes' stage or tumour differentiation. Patients with Ki-ras mutations had a marginally shorter survival time (median 50 months) compared with patients without (median 59 months), but the difference was not statistically significant. The results indicate that Ki-ras gene mutations have no relevant prognostic importance in this cohort of colorectal cancer patients.

Adult↗
PubMed1998

Smoking and the risk of leukemia, lymphoma, and multiple myeloma (Sweden).

While several epidemiologic studies have indicated a link between smoking and the risk of developing hematolymphoproliferative cancers (chiefly leukemias, lymphomas, and multiple myelomas), in particular myeloid leukemia, the role of tobacco in the etiology of these neoplasms remains unclear. To evaluate the potential impact of tobacco use on development of leukemia, lymphoma, and multiple myeloma, we conducted a cohort study of 334,957 Swedish construction workers using prospectively collected exposure-information with complete long-term follow-up. A total of 1,322 incident neoplasms occurred during the study period, 1971-91. We found no significant association between smoking status, number of cigarettes smoked, or duration of smoking and the risk of developing leukemias, lymphomas, or multiple myeloma. There was a suggestion of a positive association between smoking and the risk of developing Hodgkin's disease, although the rate ratios were not significantly elevated, except for young current smokers. No positive dose-risk trends emerged. Our study provides no evidence that smoking bears any major relationship to the occurrence of leukemias, non-Hodgkin's lymphomas, or multiple myeloma.

Adolescent↗
PubMed1998

Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer.

Serum p53 antibody levels were analysed using an enzyme-linked immunosorbent assay in serum samples obtained before surgery from 184 consecutive patients with primary colorectal cancer. Possible associations with tumour stage and tumour differentiation and the relation to patient survival time after a median follow-up of 6 years were studied. Analysis of serum p53 antibodies in the entire material demonstrated prognostic value in univariate analysis (P = 0.02); a finding that did not remain (P = 0.07) when the Dukes' stage was included in a multivariate analysis model. When the survival analysis was restricted to the potentially cured patients in Dukes' stages A-C, the serum p53 antibody levels retained independent prognostic value (P = 0.03). No clear association with tumour differentiation was found. We conclude that analysis of serum p53 antibodies may be of value for the identification of patients with different prognoses. This may be of relevance for selection of patients for adjuvant treatment.

Adult↗
PubMed1998

Benign anal lesions, inflammatory bowel disease and risk for high-risk human papillomavirus-positive and -negative anal carcinoma.

A central role in anal carcinogenesis of high-risk types of human papillomaviruses (hrHPV) was recently established, but the possible role of benign anal lesions has not been addressed in hrHPV-positive and -negative anal cancers. As part of a population-based case-control study in Denmark and Sweden, we interviewed 417 case patients (93 men and 324 women) diagnosed during the period 1991-94 with invasive or in situ anal cancer, 534 patients with adenocarcinoma of the rectum and 554 population controls. Anal cancer specimens (n = 388) were tested for HPV by the polymerase chain reaction. Excluding the 5 years immediately before diagnosis, men, but not women, with anal cancer reported a history of haemorrhoids [multivariate odds ratio (OR) 1.8; 95% confidence interval (CI) 1.04-3.2] and unspecific anal irritation (OR 4.5; CI 2.3-8.7) significantly more often than controls. Women with anal cancer did not report a history of benign anal lesions other than anal abscess to any greater extent than controls, but they had used anal suppositories more often (OR 1.5; CI 1.1-2.0). Patients with hrHPV in anal cancer tissue (84%) and those without (16%) reported similar histories of most benign anal lesions, but anal fissure or fistula was more common among hrHPV-positive cases. Ulcerative colitis and Crohn's disease, reported by <1% of study participants, were not associated with anal cancer risk. The higher proportion of hrHPV-positive anal cancers among case patients with anal fissure or fistula suggests that such mucosal lesions may provide direct viral access to basal epithelial layers. Since risk associations with benign anal lesions in men may be confounded by unreported sexual behaviour, and since risk associations in women were generally negative, it seems unlikely that benign anal lesions act as promoters in hrHPV-associated anal carcinogenesis. Moreover, benign anal lesions appear not to be linked to an alternative, hrHPV-unassociated causal pathway to anal cancer. Ulcerative colitis and Crohn's disease were not supported as causal factors for anal cancer.

Abscess↗
PubMed1998

Improved survival in patients with rectal cancer: a population-based register study.

BACKGROUND: Between 1985 and 1989, only one centre in Sweden combined preoperative radiotherapy with total mesorectal excision (TME) in the primary treatment of rectal cancer. The aim of this study was to investigate whether this change in primary treatment had an impact on the outcome. METHOD: The survival rate of 94,262 patients with colorectal cancer from the total Swedish population between 1960 and 1989 was analysed. RESULTS: A continuous improvement in relative survival rate occurred during the first year of follow-up for both colonic and rectal cancer. Some improvement was also seen during follow-up years 2-5, but this was much more pronounced during the last period (1985-1989) for rectal cancer in the county of Uppsala. The improvement was particularly marked during follow-up years 3-5. CONCLUSION: There are strong indications from this study that altered primary treatment for rectal cancer results in improved long-term survival.

Combined Modality Therapy↗