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Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 271 records · Page 15Linked to original sources

Preoperative serum markers in carcinoma of the rectum and rectosigmoid. II. Prediction of prognosis.

The prognostic value of a single preoperative determination of the serum (S) concentration of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and the carcinoma-associated carbohydrate antigen CA-50, either alone or in combination was evaluated in 327 consecutive patients with carcinoma of the rectum. A strong correlation was found between the serum level of each of these tumour markers separately, and prognosis, both in terms of crude survival in all patients and in disease-free survival in 'potentially cured' patients. The prognostic information provided by S-TPA and S-CA-50 was stronger, however, than that given by S-CEA. In a multivariate approach, S-TPA was found to be most informative. With use of the Cox regression model, the critical serum values that best separated patients in regard to mortality were CEA 18 micrograms/l, TPA 120 U/l and S-CA-50 40 U/ml. The critical values that best discriminated disease-free survival in 'potentially cured' patients were CEA 12 micrograms/l, TPA 110 U/l and S-CA-50 28 U/ml. The clinical usefulness of these and other cut-off levels is discussed.

Adult↗

Radiation therapy in upper GI tract tumours.

Radiation therapy, with or without chemotherapy, may at moderate dose levels palliate more than half of the patients with unresectable upper gastrointestinal cancer. It appears as if this therapy prolongs the median survival in these patient groups, particularly if concomitant chemotherapy is given for at most a few months. However, controlled studies are lacking. Extremely few patients will be long-term disease-free survivors even if higher dose levels are used. Since local recurrences are common after apparently radical surgery, additional radiotherapy could increase the number of long-term survivors provided the dose level is sufficiently high. This has, however, never been properly investigated. Apart from palliation in symptomatic patients with non-resectable disease, radiation therapy should be "investigational", preferably in comparison with a "no-active treatment" arm. The effects of combinations of radiation and chemotherapy should be the object of further controlled studies. Local non-resectable disease is a major problem in all upper gastrointestinal tumours. It is common both primarily and after apparent radical surgery and it causes much suffering for these patients. Radiotherapy is a local therapy and has therefore gained considerable interest in these diseases. The possibilities of contributing significantly to the treatment is, at least to a certain extent, hampered by several factors, such as the often large size of the tumour and the radiosensitivity of the surrounding tissues.

Biliary Tract Neoplasms↗

Preoperative clinical and pathological variables in prognostic evaluation of patients with rectal cancer. A prospective study of 327 consecutive patients.

The prognostic information provided by a number of easily identified and preoperatively available characteristics was recorded prospectively and evaluated in 327 consecutive patients with rectal carcinoma. With use of the Cox regression model, the two variables indicating surgical non-curability, namely immobility of the tumour to the adjacent tissues and preoperatively diagnosed metastatic spread, showed the strongest relation to prognosis. Other variables predictive of a poorer outcome in all patients were abnormal liver function tests, large tumour size (number of degrees of the bowel wall circumference affected by the tumour), non-polypoid tumour growth, tumour ulceration, tumour stricture, tumour growth anteriorly and low histological differentiation in the preoperative biopsy. These variables, together with age, also gave information concerning the group of patients of interest for pre- or peroperatively initiated adjuvant therapy, i.e. patients potentially curable by surgery (locally resectable tumour and no known metastases). In this group, the two preoperatively available variables with the best prognostic value, polypoid tumour growth and age, appeared inferior to the postoperatively determined tumour stage (Dukes' staging). However, some clinical variables gave information additional to that provided by the tumour stage.

Adult↗

Radiation therapy of anal epidermoid carcinoma.

Between 1978 and 1984, 44 consecutive patients with anal epidermoid carcinoma were either given radiation therapy alone (cloacogenic type) or in combination with Bleomycin (squamous type). The patients with small tumors (T1-T2) were treated to 65 Gy or 60 Gy + Bleomycin directly, whereas patients with moderately advanced tumors (T3) were treated to the same radiation dose, only if no evidence of residual disease existed after 50-55 Gy (40-45 Gy + Bleomycin); if a palpable tumor still remained 3 weeks after the irradiation, surgery was performed. Patients with tumors in Stage T4 were treated to 60-65 Gy (+/- Bleomycin) followed by surgery. The outcome has so far been excellent. All but four patients, treated according to the regimen and with no initial metastases, are alive and well; two died postoperatively, one developed urinary bladder recurrence, and one liver metastases. Nineteen patients have a preserved anal function. Only one of the 9 patients also treated with an abdomino-perineal excision had viable tumor at surgery. It is concluded that patients with an anal carcinoma can be safely treated with preservation of the anus in a significant proportion of the cases, and that a combined treatment approach most likely improves survival.

Adult↗

Antigenic heterogeneity and individuality in adenocarcinomas of the rectum and their secondaries.

The reaction patterns of eight antibodies directed against blood group substances A, B and H, respectively, against Lewis B antigen, difucosylated carbohydrate antigens (DFCA), gastrointestinal cancer antigen CA 19-9 (GICA), carcinoma-associated antigen CA-50 and CEA, were studied in 68 rectal carcinomas using the avidin-biotin-peroxidase method. A pronounced intratumoral antigenic heterogeneity was revealed for most antigens. It thus became evident that an interpretation based upon small preoperative biopsies would be inaccurate. The overall proportion of positive carcinoma cells, however, did not vary much between larger samples taken postoperatively from different regions of the tumours. The intertumoral antigenic variability was also considerable: nearly all tumours had an individual immunohistochemical profile according to the proportions of positive cells. Heterogeneous staining patterns were also present within metastases, and lymph node metastases from the primary tumour in some cases differed completely from each other. The staining pattern did not correlate with Dukes' stage, and degree of differentiation; the expression of any individual antigen, or several antigens in combination.

ABO Blood-Group System↗

Reversal of a developmental restriction in neural crest-derived cells of avian embryos by a phorbol ester drug.

Neural crest cells and some of the crest-derived cells of dorsal root ganglia (DRG) of early avian embryos give rise to pigment cells when placed in culture. DRG from older embryos, however, fail to do so under comparable culture conditions. This age-dependent loss of melanogenic ability might be explained either by the death of a subpopulation of latent melanoblasts within early DRG, or the imposition of additional developmental restrictions in multipotent DRG cells. We show here that 12-O-tetradecanoylphorbol-13-acetate (TPA) causes some DRG cells to undergo pigmentation in cultures from older embryos, indicating that the loss of melanogenic ability in older embryos is not due to cell death. These pigment cells also display morphogenetic properties of normal melanocytes, including the ability to invade feather primordia. In addition to DRG, various other neural crest-derivatives contain cells similarly affected by TPA, including cells within sympathetic ganglia and peripheral nerves. We suggest that TPA reverses the developmental restriction of melanogenic ability that is normally imposed on neural crest-derived cells that migrate to various sites in avian embryos where melanogenesis does not normally occur.

Animals↗

Sequential methotrexate--5-FU--leucovorin (MFL) in advanced colorectal cancer.

Methotrexate (MTX) (250 mg/m2) was given as an i.v. infusion over 2 hr. At hour three and 23, 5-FU (500 mg/m2, maximally 1000 mg) was given as a bolus i.v. injection. The Leucovorin rescue was initiated hour 24. The chemotherapy course was repeated every 14 days for eight courses, then every third to fourth week. At least four courses of the regime were given to 50 patients with measurable advanced colorectal carcinoma. Toxicity was usually very mild but in seven patients an increase of serum creatinine was registered. Two of these patients had a severe period of uremia. With a more careful observation of kidney function, these episodes should have been foreseen. An objective response rate of 50% with six complete remissions (CR) and 19 partial remissions (PR) was found. Eighty-eight per cent (21/24) of the patients with tumour-related symptoms experienced symptomatic relief. The median response duration amounts to 5 months. It is concluded that the MFL regime is effective in inducing anti-tumour response in patients with advanced colorectal cancer.

Adult↗

Pre- versus postoperative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial.

Since October 1980 a randomized multicentre trial has been in progress among patients with rectal carcinoma, in whom high-dose fractionated pre-operative irradiation (total dose 25.5 Gy in 5-7 days) is being tested against postoperative irradiation to a high dose level using a conventional fractionation scheme (totally 60 Gy in 8 weeks) delivered only to a high-risk group of patients (Dukes' stages B and C). The primary aim of the trial is to investigate whether local recurrence rate differs between the two groups, and a secondary aim is to see whether 5-year survival will differ between the two groups of patients. Up to October 1984, 360 patients have been randomly allocated to these two groups. Locally curative surgery has been performed in 161 patients in the pre-operative irradiation group and in 152 patients in the postoperative irradiation group. Pre-operative irradiation was extremely well tolerated and there were no irradiation-related complications; 95 per cent of these patients received their treatment according to the intended schedule. However, 48 of the 161 patients had a tumour in Dukes' stage A. Pre-operative radiotherapy had no impact on postoperative mortality or the occurrence of anastomosis dehiscence, but significantly more patients with perineal wound sepsis after an abdominoperineal resection were found in the group of patients receiving pre-operative radiotherapy. This prolonged the stay in hospital after surgery. Postoperative radiotherapy was not so well tolerated as pre-operative treatment, and in a substantial number of patients the treatment could not be commenced until a relatively long time after surgery. To date, the local recurrence rate is acceptably low (approximately 10 per cent) in both treatment groups.

Clinical Trials as Topic↗

CHOP vs MEV for the treatment of non-Hodgkin's lymphoma of unfavourable histopathology: a randomized clinical trial.

The Swedish Lymphoma Study Group has compared the results of treatment with a CHOP regimen (cyclophosphamide, adriamycin, vincristine and prednisone) with those of treatment with a MEV regimen (methotrexate, cyclophosphamide and vincristine) in patients suffering from generalized non-Hodgkin's lymphoma (NHL) of unfavourable histopathology in a prospective randomized trial. The complete remission rate for 67 evaluable patients receiving CHOP was higher (61%) than for 74 patients receiving MEV (24%) (P less than 0.001). The relapse rate was 18/41 (44%) in the CHOP group and 11/18 (61%) in the MEV group (difference not significant). At follow-up the number of patients alive in a first complete remission was thus 23/67 in the CHOP group but only 7/74 (9%) in the MEV group. This difference is highly significant (P less than 0.001). However, there is still no significant difference in overall survival between the two treatment groups. This is probably due to the more efficient rescue treatment (mainly CHOP) found in the patients who primarily received MEV than in those who primarily received CHOP. It is concluded that the CHOP regimen is superior to the MEV regimen in NHL patients with unfavourable histopathology.

Adult↗

Alpha interferon treatment of patients with hairy-cell leukaemia.

We have treated 10 patients with hairy-cell, or hairy-cell-like leukaemia, for more than 6 months, with alpha interferon 3 X 10(6) IV/day I.M. or subcutaneously. All patients were severely pancytopenic before treatment. 7 patients had a typical hairy-cell leukaemia, whereas 3 lacked hairy cells but had the characteristic bone-marrow infiltration. The peripheral blood counts improved in all patients during treatment and the lymphoid infiltration of the bone-marrow was shown to decrease. 1 patient obtained complete remission, 6 partial remission and 3 had a minor response. It is concluded that alpha interferon is effective in the treatment of patients suffering from hairy-cell leukaemia.

Aged↗

DNA content in carcinoma of the rectum and rectosigmoid.

Using single cell cytometry the pattern of DNA content in preoperative samples from 131 carcinomas of the rectum and rectosigmoid has been studied. For comparison, 21 carcinomas of the colon, 44 colorectal polyps and mucosa adjacent to the tumours were also included. The biopsies were classified into near diploid (ND), near diploid with aneuploid cells (ND-anc) and aneuploid (AN). A more specific subclassification of aneuploid samples was not consistent because of a commonly occurring multiclonality, where different clones dominated different parts of the tumours. Fifteen of all 130 representatively sampled rectal carcinomas were ND; however, all the ND scores were based on a single sample. Among 31 multiply-sampled carcinomas none registered as ND in all samples. There were no principal differences in patterns of DNA profiles between rectal and colon carcinomas. Five samples from the pericancerous mucosa and samples from 4 adenomas showed non-ND patterns, which may be a premalignant sign. The main conclusions of these results are that rectal carcinomas, even if they contain a substantial ND cell population, to a very great extent contains cells with an abnormal DNA content. The carcinomas can be classified according to their pre-operatively estimated DNA content. The clinical relevance of this will be judged when the patients have been followed for longer time periods.

Adenocarcinoma↗

Excision biopsy of the spleen by ultrasonic guidance.

Excision biopsy of the spleen was performed in 32 patients, using a recently invented instrument, which consists of a spring-trigger system for firing the two parts of a Tru-Cut needle. The biopsies were carried out under the guidance of an ultrasonic scanner. This technique yields sufficient material of high quality for a proper evaluation both of individual cells and the internal structure of the spleen. Eight patients had parenchymal abnormalities found by ultrasonic scanning: five had multiple abnormalities whereas three had a single abnormal area. Seven of these eight patients had a pathological spleen biopsy, consisting of Hodgkin's disease (four patients), "high-grade" malignant non-Hodgkin's lymphoma (two patients) or tuberculosis (one patient). In the other 24 patients with a normal ultrasonic picture of the splenic parenchyma five biopsies were pathological (3 cases of hairy-cell leukaemia, 1 of Gaucher's disease and 1 of Hodgkin's disease). Side-effects were: slight to moderate pain (16/32 patients) and bleeding requiring transfusion (4/32 patients). In one of these patients splenectomy was performed because of the bleeding. Two of the patients with bleeding complications suffered from hairy-cell leukaemia. It is concluded from this study that excision biopsy of the spleen is a diagnostic method which in some patients can replace splenectomy. The method seems to be valuable especially in patients with parenchymal abnormalities shown by ultrasonic scanning.

Adolescent↗

Clinical characteristics and their relation to surgical curability in adenocarcinoma of the rectum and rectosigmoid. A population-based study on 279 consecutive patients.

Between January 1980 and December 1982, 221 patients with rectal or rectosigmoid carcinoma were admitted from a defined population to one department of surgery in Sweden. In addition, all patients with a rectal tumour were traced in the population, and in this way 83 additional cases were recorded. A total of 304 malignant lesions were diagnosed and 279 (92%) of them were adenocarcinoma. The surgical curability rate in this unselected material of adenocarcinoma of the rectum and rectosigmoid, defined as the proportion of patients operated upon for cure with respect to both local radicality of surgery and absence of indications of disseminated disease, was 60%. Age (greater than or less than 80 years) but not sex had a major influence on the rate of surgical curability. Weight loss and pain, and also more than two tumour-related symptoms at presentation, were more common among patients with noncurable disease. A short diagnostic delay correlated to a more favourable tumour stage.

Adenocarcinoma↗

A chondroitin sulphate proteoglycan from human cultured glial and glioma cells. Structural and functional properties.

A chondroitin sulphate proteoglycan capable of forming large aggregates with hyaluronic acid was identified in cultures of human glial and glioma cells. The glial- cell- and glioma-cell-derived products were mutually indistinguishable and had some basic properties in common with the analogous chondroitin sulphate proteoglycan of cartilage: hydrodynamic size, dependence on a minimal size of hyaluronic acid for recognition, stabilization of aggregates by link protein, and precipitability with antibodies raised against bovine cartilage chondroitin sulphate proteoglycan. However, they differed in some aspects: lower buoyant density, larger, but fewer, chondroitin sulphate side chains, presence of iduronic acid-containing repeating units, and absence (less than 1%) of keratan sulphate. Apparently the major difference between glial/glioma and cartilage chondroitin sulphate proteoglycans relates to the glycan rather than to the protein moiety of the molecule.

Cells, Cultured↗