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Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 163 records · Page 9Linked to original sources

Monitoring palliative chemotherapy in advanced gastrointestinal cancer using serial tissue polypeptide specific antigen (TPS) measurements.

Tissue polypeptide antigen specific (TPS) was analysed in serum taken prior to chemotherapy in 90 patients with advanced gastrointestinal cancer and prior to every treatment course in 68 of these patients in order to explore whether serial tumour marker measurements can be of importance in monitoring patients treated with palliative chemotherapy. Elevated TPS levels were seen in 83/90 (92%) patients (48/52 colorectal, 9/9 pancreatic, 9/11 biliary, 17/18 gastric). Baseline TPS level correlated with performance status, tumour response and survival. Based upon the change in TPS levels after the first two courses in relation to baseline, a decrease by >50% had a high sensitivity for a favourable treatment outcome (partial remission and prolonged stationary disease (90%) or a subjective response (100%)), whereas the specificity was lower (72% and 73% respectively). A similar result was seen when the TPS levels were analysed at the time of the response evaluation after 2 months (sensitivity 91 and 95%, specificity 74 and 75% for an objective or subjective response respectively). In 7 out of 15 patients with an initially favourable outcome, an increase in TPS levels of >50% at two occasions was seen 8-20 weeks prior to clinical disease progression. In advanced gastrointestinal cancer serial TPS measurements can with high accuracy early identify patients who will not benefit from the treatment. On the other hand, a response must be confirmed using other methods in the presence of a decrease, since this was also seen in non-responding patients.

Adult↗

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for non-Hodgkin's lymphomas: a Swedish national prospective study. Swedish Lymphoma Study Group.

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.

Adult↗

Different intravenous administration techniques for 5-fluorouracil. Pharmacokinetics and pharmacodynamic effects.

The pharmacokinetics after 20 min intravenous infusion or a 2 min bolus (push) injection of 5-fluorouracil (500 mg/m2) were studied in 14 colorectal cancer patients. Treatment effects and toxicity related to the administration technique of 5-fluorouracil were retrospectively analysed in 198 colorectal cancer patients. The AUC after bolus injection was 6158 +/- 874 micromol/l*min compared to 3355 +/- 428 micromol/l*min after short-time infusion of 5-fluorouracil (p < 0.01). The mean peak-level after bolus injection was 341 +/- 34 microM versus 161 +/- 17 microM after a short-time infusion (p < 0.01). Patients receiving bolus injections had significantly better treatment result (32% partial remission) than patients receiving infusion (10% partial remissions, p < 0.001). Toxic side-effects were more frequently encountered after bolus injection but subjective improvement was also more frequently experienced by these patients. Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique.

Aged↗

Anxiety, depression and worry in gastrointestinal cancer patients attending medical follow-up control visits.

Anxiety, depression and worry were assessed in 141 consecutive gastrointestinal cancer patients scheduled for follow-up control visits. Participants completed two questionnaires, one including the Hospital Anxiety and Depression Scale (HAD) in conjunction with the visit and one completed after. The overall levels of anxiety before, during and after the visit were low. There were no differences between those who were considered cured and those who were not. Anxiety levels after the visit were higher for those patients for whom less than one year had passed since diagnosis. Mean HAD scores for anxiety and depression were 4.2 and 4.3 respectively. Women reported a higher degree of anxiety than men. Using a score of 8 or more for 'borderline-possible cases', 15% fell into these categories on the anxiety scale and 12% on the depression scale. About 30% of the patients worried about seeing a new physician and 25% about what the examination or tests would show. It is concluded that regular, scheduled control visits pose a significant threat to the psychological well-being of only a minority of gastrointestinal cancer patients.

Adaptation, Psychological↗

Treatment of Hodgkin's disease: the Swedish National Care Programme experience.

Since 1985 a Swedish National Care Programme has provided tailored principles for the diagnosis, staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report gives the rationale behind the recommendations and presents treatment results for 648 patients diagnosed between 1985 and 1989 after a median follow-up of 70 months. Two hundred and twenty-nine (35%) patients were over 60 years of age. Treatment results for patients below 60 years of age in early and intermediate stages were favourable, provided the recommendations were followed. In advanced stages, the outcome was inferior in patients with CS IIB bulky disease and stage IVB. The prognosis of elderly patients remains poor, although it is too early to evaluate any impact of revisions made in 1989. The tailored principles, which usually entail less staging and/or treatment than is generally the case in the early and intermediate stages, produced favourable results when applied to an unselected group of patients with HD. Only minor changes were made in the recommendations during the 1994 revision.

Adolescent↗

A novel human B-cell line (U-2904) bearing t(8;14) and t(14;18) translocations.

Sequential activation of bcl-2 and c-myc appears to be involved in the pathogenesis of rare de novo acute lymphoid leukemias bearing both t(8;14) and t(14;18). Acquisition of t(8;14) by follicular-lymphoma cells with t(14;18) has also been related to the clinical transformation into an overt acute lymphoid leukemia in rare cases reported, and a role for c-myc involvement in the progression of some follicular lymphomas with t(14;18) has been suggested by the detection of c-myc rearrangements in association with histologic transformation. However, c-myc abnormalities different from those observed in Burkitt's lymphoma have been reported in diffuse large-cell lymphomas with breakpoints in 8q24, and a t(8;14) molecularly different from the classical one has been found in follicular lymphomas without t(14;18). We report the preliminary characterization of the EBV-negative cell line U 2904 established from a transformed follicular lymphoma that carries both t(8;14) (q24;q32) and t(14;18) (q32;q21) translocations. U 2904 cells have a mature B-cell phenotype, grow in agarose and are tumorigenic in nude mice. Rearrangements of both c-myc and bcl-2 confirmed the involvement of both oncogenes in the translocations which lead to abundant c-myc and bcl-2 transcripts. Two JH rearrangements and one C alpha rearrangement were observed which did not co-migrate with either c-myc or bcl-2 rearrangements. This is the first report of a cell line bearing both t(8;14) and t(14;18) derived from a follicular lymphoma after documented transformation into a centroblastic lymphoma without leukemic features. U 2904 provides further evidence for the involvement of c-myc in the progression of follicular lymphomas.

Animals↗

Selective sensitivity of solid tumors to suramin in primary cultures of tumor cells from patients.

The antineoplastic activity of suramin is currently the subject of clinical trials. We therefore used the semi-automated fluorometric microculture cytotoxicity assay (FMCA) to evaluate the cytotoxicity of suramin in vitro in primary cultures of cells from patients with hematological or solid tumors. The activity patterns of some standard cytotoxic agents were included for comparison. A total of 159 samples were tested using continuous drug exposure. Suramin showed relatively high activity against solid tumors, with colorectal, adrenal and kidney carcinomas being the most sensitive, whereas hematological malignancies were more resistant. Suramin and standard drugs showed very low cross-resistance. The results indicate that suramin is differentially active against some solid tumors with comparatively little activity against hematological tumors. The study provides an experimental motive for evaluation of suramin therapy in patients with solid tumors and exploration of less toxic suramin analogues.

Antineoplastic Agents↗

Evidence of an association between non-Hodgkin's lymphoma and skin cancer.

OBJECTIVE: To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkin's lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non-Hodgkin's lymphoma and skin cancer was studied. DESIGN: Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. SETTING: Denmark (1943-89) and Sweden (1958-89). SUBJECTS: Four population based cohorts identified in the nationwide cancer registries (34,641 people with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukaemia, 34,989 with malignant melanoma, 25,980 with squamous cell skin cancer). A total of 562,085 person years were accrued for the analysis. MAIN OUTCOME MEASURES: The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. RESULTS: The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non-Hodgkin's lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non-Hodgkin's lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. CONCLUSIONS: The occurrence of non-Hodgkin's lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkin's lymphoma in recent decades.

Age of Onset↗

Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma.

BACKGROUND: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.

Aged↗

Treatment of local recurrences of rectal carcinoma.

From 1978-1992, 159 patients were treated for local recurrences of rectal carcinoma. They could be subdivided into three groups according to the type of primary treatment given; 82 patients underwent primary surgery without irradiation, 37 patients had preoperative and 40 patients postoperative radiotherapy. The localizations of the recurrences and the curative and palliative potentials of surgery and radiotherapy in the treatment of local recurrences were studied. There was no difference in the localisation of the recurrences in the three groups. Median time between initial surgery and recurrence was also almost the same in the three groups and 75% of the recurrences appeared within 2 years. Twenty percent of the patients in the primary surgery alone group, compared with 49% and 38% in the preoperative and postoperative irradiation groups, respectively, had distant metastases at the time of the diagnosis of local recurrence. The predominant symptom from the local recurrence was pain and, after treatment of the recurrence, pain relief was registered in 63%. In 66%, 16% and 22%, respectively, of the patients in the three groups, the intention of the treatment was curative, with either radiotherapy alone, radiotherapy combined with surgery or surgery alone. The 5-years-survival after recurrence was 6% in the primary surgery alone group and 0% in the other 2 groups. Of the 69 patients treated with a curative intention, 32% were locally symptom-free at death or the last follow-up. Our conclusion is that a local recurrence must be avoided due to the morbidity associated with local failure and the potentially low likelihood of curative treatment of a local recurrence.

Adult↗

Information to and communication with cancer patients: improvements and psychosocial correlates in a comprehensive care program for patients and their relatives.

Between 1987 and 1989, 177 cancer patients who were to receive intensive chemotherapy with curative intention, participated in a comprehensive care project with the aim of improving their total situation, and that of their relatives (n = 120). A number of steps were taken to improve, among other things, the information to, and communication with, patients and their relatives. Compared with a pre-project evaluation in 54 patients and 24 relatives, significantly lower problem scores were seen in most aspects relating to interaction with medical staff. Strong associations were seen between, on the one hand, various aspects of patient- and relative-staff interaction and, on the other, psychosocial problems, although they were weaker for problems relating to information, than for communication and control problems.

Communication↗

The association of preoperative serum tumour markers with Dukes' stage and survival in colorectal cancer.

The tumour markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), TPS, CA 19-9, CA 50 and CA 242 were analysed in serum from 203 potentially curable colorectal cancer patients. The levels of all markers increased with increasing tumour stage, and all markers correlated with survival. Multivariate analyses indicated that the Dukes stage had the best prognostic explanatory power, followed by TPA. In the subset of 166 potentially cured patients, the prognostic information by the markers was substantially reduced. We conclude that preoperative serum tumour marker measurements have the potential to aid therapy selection, but also that their clinical usefulness is not immediately apparent.

Adult↗

Deoxythymidine kinase in the tumour cells and serum of patients with non-Hodgkin lymphomas.

The levels of deoxythymidine kinase in tumour cells (C-TK) and in serum (S-TK) were investigated and the tumour volume calculated in 89 patients with non-Hodgkin lymphoma (NHL), in order to ascertain the importance of C-TK and tumour burden as regards the S-TK levels. Among all patients, a correlation was seen between S-TK and tumour volume but not between S-TK and C-TK. However, within different tumour volume categories (small, medium-sized and large), there was a correlation between S-TK and C-TK. Multiple regression analysis supported this notion. C-TK correlated with the proliferation-associated parameters, S-phase fraction and mitotic index. As already known, S-TK was found to have a strong prognostic value. C-TK and tumour burden were also of prognostic value. In multivariate analyses, C-TK and tumour volume did not provide prognostic information in addition to S-TK, whereas, in the absence of S-TK, C-TK and tumour volume did provide additional information. It is concluded that the serum level of TK depends on both the tumour burden and the tumour cell proliferation rate. Based upon estimations of S-TK in patients assessed shortly after chemotherapy, we also suggest that S-TK reflects the number of proliferating cells that have died during the period immediately before sampling.

Cell Division↗

The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL.

In patient tumour samples the activity in vitro of Taxol corresponded fairly well to the known clinical activity and Taxol showed low cross-resistance to standard cytotoxic drugs. However, the Taxol solvent Cremophor EL--ethanol was considerably active alone, whereas paclitaxel formulated in ethanol was less active. Taxol thus seems to contain two components active against patient tumour cells in vitro.

Antineoplastic Agents↗

Serum levels of interleukin-2 receptor (CD 25) in patients with Hodgkin's disease, with special reference to age and prognosis.

BACKGROUND: The serum levels of soluble interleukin-2 receptor (S-sIL-2R) have been shown to be related to clinical outcome in Hodgkin's disease (HD). sIL-2R may be involved in or aggravate the immunodeficiency seen in HD patients. This immunodeficiency is most pronounced in elderly patients. PATIENTS AND METHODS: S-sIL-2R was determined in 127 untreated patients with HD, diagnosed between 1979 and 1991, in order to evaluate its prognostic value in relation to other known prognostic variables with special emphasis on the elderly. RESULTS: S-sIL-2R levels were significantly higher in patients with stages III-IV and with B-symptoms (p < 0.001) but not in patients over 60 years of age. In multivariate analyses, S-sIL-2R, stage and S-orosomucoid were the most important prognostic factors in all patients and S-sIL-2R was the only prognostic factor in patients over the age of 60. CONCLUSIONS: The results indicate a future role for estimation of S-sIL-2R in the management of patients with HD.

Adolescent↗

Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer.

BACKGROUND: Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy. PATIENTS AND METHODS: Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed. RESULTS: More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients. CONCLUSIONS: The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.

Adult↗

Radiotherapy in addition to radical surgery in rectal cancer.

In order to lower unacceptably high local failure rates after surgery reported as curative for rectal cancer, perioperative radiotherapy has been extensively investigated. The collected information from a number of controlled trials indicates that the proportion of local recurrences is reduced to less than half when radiotherapy at moderately high doses is given preoperatively. This reduction in local failure rates is not seen after postoperative radiotherapy, even if higher doses have been used. Possibly, there is also a slight positive influence on survival from preoperative radiotherapy. Improved survival has been seen also in trials using postoperative radiotherapy, but then only when combined with chemotherapy. With proper dose planning, sufficiently high doses can be given preoperatively with little if any increase in postoperative mortality. Thus, although published knowledge is still rather limited, a properly planned preoperative radiotherapy seems to inflict small bowel and other complication rates, that are less than when radiotherapy of similar efficacy against the tumour is given postoperatively.

Combined Modality Therapy↗