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Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 253 records · Page 14Linked to original sources

Preoperative irradiation with and without chemotherapy (MFL) in the treatment of primarily non-resectable adenocarcinoma of the rectum. Results from two consecutive studies.

Twenty-one consecutive patients with primarily non-resectable adenocarcinoma of the rectum were treated with preoperative split-course radiotherapy (40 Gy) and simultaneous sequential methotrexate + 5-fluorouracil + leucovorin (MFL). An initial infusion of methotrexate (250 mg/m2) was followed in the 2nd hour by 5-FU--first a bolus injection (10 mg/kg) and then continuous infusion (35 mg/kg/24 h) for 72 h. Leucovorin rescue (15 mg every 6 h) was initiated 24 h after the initial injection. Radiotherapy (10 Gy) was given with two 2.0 Gy fractions on days 1 and 2, and one fraction on day 3. The toxicity of the treatment was mostly mild to moderate. Compared with a previous consecutive series comprising 38 patients who received preoperative irradiation (greater than or equal to 40 Gy) only, with a resectability rate of 34%, the 71% resectability rate with this treatment seems to be superior.

Adenocarcinoma↗

Primarily asymptomatic low-grade non-Hodgkin lymphomas: prediction of symptom-free survival and total survival.

Low-grade non-Hodgkin lymphomas (NHL) constitute a group of tumours with an often long survival time but, at present, with little--or no--chance of cure if the disease is not strictly local. In primarily asymptomatic patients, treatment may either be started immediately after diagnosis or deferred until symptoms occur. The possibility of predicting the symptom-free time was investigated in 64 non-selected initially asymptomatic patients with advanced low grade NHL, all of whom had treatment deferred until symptoms occurred. The most powerful predictor was the histopathological subgroup. Lymphocytic (LC) and follicular centroblastic-centrocytic (fCBCC) lymphomas had a median symptom-free period of 2 years, which was four times longer than that for immunocytoma (IC) and follicular and diffuse CBCC (fdCBCC). In addition, the serum levels of deoxythymidine kinase (S-TK) and lactic dehydrogenase (S-LDH) could predict the symptom-free period. This did not apply to S-Haptoglobin, S-Orosomucoid or stage. In a multivariate analysis, only S-TK gave additional information to histopathology. The only variable that predicted the overall survival time was the length of the symptom-free period.

Follow-Up Studies↗

Immunophenotype analysis of B-CLL lymphoma and immunocytoma.

The differential diagnosis between lymphocytic lymphoma of the B-CLL type and immunocytoma (IC) can be difficult when it is based only upon morphological criteria. With the aim of improving the distinction between these subgroups, frozen sections of lymph nodes or other biopsied tissues from 14 cases of B-CLL and 16 cases of IC were investigated according to immunophenotype. A panel of 13 B cell-associated and 2 T cell-associated monoclonal antibodies was used. All but one of the B-CLL cases were FMC7-, while 14/16 IC cases were FMC7+ (p less than 0.001). The two negative IC cases were both of the lymphoplasmacytic type, claimed to be "more differentiated" than the lymphoplasmacytoid type. We suggest that the cells in these cases are mature enough to have lost their FMC7 positivity, similar to plasma cells. There was also a statistically significant (p less than 0.01) difference, although not as pronounced, for the anti-CD38 antibody (Leu-17, B-CLL: 3/14, IC: 10/16 positive). No significant difference in expression of determinants was found for any of the other antibodies.

ADP-ribosyl Cyclase↗

Can mortality from rectal and rectosigmoid carcinoma be predicted from histopathological variables in the diagnostic biopsy?

The prognostic information provided by histopathological variables in the diagnostic biopsy was evaluated retrospectively in 276 consecutive patients "potentially curable" by surgery using criteria recently proposed by Jass et al. concerning the main specimen. In 252 (91%) cases, the biopsy material was appropriate for the intended assessment. The majority of tumours were tubular (67%), tubular configuration mostly irregular (76%) and the tumour cells usually had small nuclei (81%). Remnants of adenomatous structures were identified in 21%. Most tumours were moderately differentiated (57%), and poorly differentiated tumours were somewhat more common (27%) than highly differentiated ones (16%). There was no real correlation between these histopathological variables, as expressed in biopsy, and Dukes' stage. Patients with a well-differentiated tumour had somewhat better survival than those with a moderately or poorly differentiated one (p = 0.04). Tumour type tended to influence cancer-specific mortality in that patients with papillary tumour had a slightly better prognosis than those with a different type. An attempt was also made to classify the patients into two groups on the basis of the observers' subjective impression of the tumour pattern and the expected outcome. Among the 143 patients in whom the over-all subjective impression was an "aggressive tumour pattern", 43% died (median follow-up 47 months). The cancer-specific death rate in patients in whom the tumour pattern was "non-aggressive" was 27% (p = 0.04). In summary, the extent to which these variables predicted mortality was far from clinically useful.

Adenocarcinoma↗

Prognostic factors in non-Hodgkin lymphoma stage I treated with radiotherapy.

The results of treatment in 175 consecutive patients with nonHodgkin lymphoma (NHL) clinical stage I treated between 1969 and 1984 were analysed according to different pretreatment prognostic variables. Treatment consisted of radiotherapy in 166 of the 175 patients. The estimated 5 and 10-year disease-free survival rates (DFS) were 63% and 60% and the survival rates at 5 and 10 years 82% and 76% respectively. Lymphomas arising from gut-associated lymphoid tissue, i.e. Waldeyer's ring, the thyroid and the gastrointestinal tract had a more favourable clinical course (10-year projected DFS 83%) than nodal (50%) and other extranodal lymphomas. Although the number of patients with other extranodal sites was small, sites such as testis, nasal cavity, paranasal sinus and extradural space seemed to have a high relapse rate. Unfavourable clinical courses were also observed among nodal high-grade NHL if the lymph nodes were larger than 5 cm in diameter. Chemotherapy before radiotherapy may be recommended in NHL subgroups with a high relapse rate and which today are potentially curable with chemotherapy, i.e. highgrade NHL. This study indicates that large nodal lymphomas and some extranodal sites belong to this group.

Adult↗

Incidence of anal epidermoid carcinoma in Sweden 1970-1984.

A retrospective study was made of 858 cases of anal epidermoid carcinoma notified to the Swedish Cancer Registry in the 15-year period 1970-1984. The mean age at diagnosis was 67 years, with 5% (45) of the patients aged 25-44, 37% (314) aged 45-64 and 58% (499) greater than or equal to 65 years. All three age groups showed female predominance (c. 2:1), and the mean annual age-adjusted incidence/100,000 population was 1.40 for women and 0.68 for men. Incidence was highest in the cities of Stockholm (1.89) and Malmö (1.53). A strongly positive correlation was found between incidence of the disease and proportion of the population living in urban areas. Substantial annual rise (mean 4.3%) in incidence occurred during the study period, approximately the same in both sexes, in all age groups and in different "risk areas".

Adult↗

Improved survival of patients with cancers of the colon and rectum?

The survival of 61,769 patients diagnosed as having colorectal cancer in the total Swedish population in 1960-1981 was analyzed. The 5-year relative survival rates during the total period were approximately 40%; patients with colonic carcinoma had a somewhat better prognosis than patients with rectal carcinoma, and men had a generally less favorable prognosis than women. Comparison of patients diagnosed in 1960-1964 and in 1975-1979 showed a slight improvement in survival during the more recent study period, i.e., an improvement rate of 7.0% for both cancer of the colon and cancer of the rectum. The improvement occurred mainly during the first months of follow-up. However, the excess mortality due to colorectal cancer 1-5 years after diagnosis as compared to the expected mortality in the general population remained virtually unaltered. A multivariate analysis in which adjustment was made for the possible confounding variables of sex, age, and site (of colonic carcinoma) gave consistent results. Reduced postoperative mortality was considered to be the most likely major explanation for the temporal trend toward a more favorable prognosis. Thus it seemed that the treatment of colorectal cancer in Sweden during the last two decades has not improved significantly except in terms of reduced postoperative mortality. Thus the challenge of improving survival in patients with colorectal cancer must be given high priority.

Actuarial Analysis↗

Anal epidermoid carcinoma: a population-based clinico-pathological study of 164 patients.

The clinical and pathological features of 164 patients with anal epidermoid carcinoma were investigated in a population-based study between 1978 and 1984. Twenty-three tumours, the majority of which were small and well differentiated squamous cell carcinomas, were situated in the perianal region. Twenty of these patients are alive and disease-free. Of 141 tumours in the anal canal two-thirds were of the cloacogenic type, i.e. displaying transitional cell differentiation. The overall 5-year survival was between 40 and 50% for both cloacogenic and squamous cell carcinomas, respectively. However, poorly differentiated squamous cell carcinomas and cloacogenic carcinomas without any squamous cell differentiation (subtype A) had a more aggressive course, especially in men, than the other subgroups. Clinical stage also had an impact on prognosis. Both stage, sex, degree of differentiation and histologic subtypes revealed independent prognostic information. Although the primary aim of this study was not to evaluate therapy, it was noted that patients primarily treated with irradiation (with or without chemotherapy) had a more favourable course than patients treated with surgery alone.

Adult↗

The expression of carcinoma-associated antigens and blood-group-related antigens in rectal carcinoids.

The immunohistochemical expression of blood-group substances and carcinoma-associated antigens were compared in rectal carcinoids and adenocarcinomas. Rectal carcinoid tumors, in contrast to rectal carcinomas, were consistently negative for CEA, gastrointestinal cancer antigen GICA (or CA 19-9), and carcinoma-associated antigen CA-50 (except in one case where less than 10 percent of the cells expressed CA-50). The carcinoids and rectal carcinomas extensively expressed blood-group substance A, B, and H, Lewis B antigen, and difucosylated carbohydrate antigens (DFCA). Thus, rectal carcinoids and adenocarcinomas possess both similar and different tumor antigen profiles. The occurrence of discrepant antigen determinants may be used in the differential diagnosis of these two types of tumors. The coexpression of blood-group substance A, B, and H, Lewis B antigen, and DFCA is consistent with the opinion that both rectal carcinomas and carcinoids have a common entoderm origin, but carcinoids are considered to rise from the endocrine-differentiated and the adenocarcinomas from the nonendocrine-differentiated enterocytes.

Adenocarcinoma↗

A clinical study of CA-50 as a tumour marker for monitoring of colorectal cancer.

Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes' A (15%), Dukes' B (43%), Dukes' C (31%) and Dukes' D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes' A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes' A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

Antigens, Neoplasm↗

CA-50 as a tumour marker for monitoring colorectal cancer: antigen rises in patients postoperatively precede clinical manifestations of recurrence.

Using a monoclonal antibody-based radioimmunoassay inhibition method we have determined preoperative serum levels of the carcinoma-associated carbohydrate antigen CA-50 in 266 patients with primary colorectal cancer. CA-50 levels exceeding the mean value for blood donor sera by more than 2 standard deviations (greater than or equal to 17 U/ml) were found in 47% of these patients, with 15%, 43% and 31% being elevated in patients with Dukes' A, Dukes' B and Dukes' C cancer, respectively, and 63% and 66% being elevated in patients with more advanced localized or disseminated cancer. Only 5% of patients with benign colorectal disease had elevated CA-50 level and these were patients with ulcerative colitis of a duration of more than 10 years. Among patients who had developed a recurrence after operation for a primary Dukes' A-C colorectal cancer 66% had elevated levels, and 25% of resected patients with no clinical evidence of disease at corresponding times after operation also had CA-50 levels above the normal concentrations. From 139 patients operated for a Dukes' A-C colorectal cancer a definitive rise in CA-50 levels from the pre- to a 6-9 months postoperative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On prolonged follow-up a clinically manifest recurrence later developed in all of these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. Our findings suggest that a rise in CA-50 levels after resection of a Dukes' A-C primary colorectal cancer is indicative of a recurrence and may precede any clinical evidence of disease by many months or years. Thus CA-50 may be a clinically useful tool for monitoring of patients with colorectal cancer.

Adenocarcinoma↗

The adenoma-carcinoma sequence in rectal adenomas. Support by the expression of blood group substances and carcinoma antigens.

The reaction patterns of eight antibodies directed against blood group substances A, B, and H and against Lewis B antigen, difucosylated carbohydrate antigens (DFCA), gastrointestinal cancer antigen (GICA) CA 19-9, carcinoma-associated antigen CA-50, and carcinoembryonic antigen (CEA) were studied in mucosa and adenomas of the rectum. Antigenic heterogeneity was a common feature of rectal mucosa and was observed to a considerable degree in adenomas. In general, the rectal mucosa expressed only a few antigens and to a limited extent. The adenomas were more extensively stained than the rectal mucosa. The proportion of positive cells increased with the grade of dysplasia but was relatively unrelated to the histologic type. The proportion of individual antigens expressed and the number of antigens extensively expressed increased between rectal mucosa, benign adenomas, and adenomas with early invasive carcinoma. These findings support the concept of an adenoma (dysplasia)-carcinoma sequence.

ABO Blood-Group System↗

Prognostic relevance of serum-markers in relation to histopathology, stage and initial symptoms in advanced low-grade non-Hodgkin lymphomas.

The prognostic relevance of 4 different serum markers (deoxythymidine kinase = S-TK, lactic dehydrogenase = S-LDH, S-Haptoglobin and S-Orosomucoid) in relation to histopathology according to the Kiel classification, stage and presence or absence of initial symptoms were investigated in 168 consecutive cases of low-grade non-Hodgkin lymphomas (NHL). All serum markers, as well as the other three parameters, gave prognostic information. Univariate analysis yielded a high predictive value (p less than 0.0002) for both S-TK and S-LDH. The best information regarding the probability of survival was, however, obtained from the presence or absence of symptoms from lymphoma manifestations other than those caused by a strictly local tumor mass. Since S-TK and S-LDH correlated well with each other, only the better of them, S-TK, gave information additional to initial symptoms in a multivariate test.

Aged↗

Extracellular matrices in multicellular spheroids of human glioma origin: increased incorporation of proteoglycans and fibronectin as compared to monolayer cultures.

Tumor spheroids were cultured from five human glioma cell lines which differed considerably in their relative amount and composition of glycosaminoglycans (GAG), fibronectin and other extracellular matrix (ECM) components when grown as monolayer cultures. These differences were also evident when the cells were grown as spheroids. Under the 3-dimensional geometry of the spheroid system, there was, however, generally a more extensive ECM. Especially noteworthy was the presence of a small proteoglycan, probably a dermatan sulphate proteoglycan, in the ECM of the spheroids, but not in the monolayers. Noteworthy was also the appearance of fibronectin in spheroids which did not show any staining for fibronectin when grown as monolayer. The two spheroid types (U-87MG, U-105MG) with the most extensive matrix, and with the lowest proportion of hyaluronic acid (HA), had a low proliferation rate, whereas the three other spheroid types (U-118MG, U-138MG, U-251MG) with a less extensive ECM, and a relatively high production of HA had a much higher proliferation rate. These data provide further evidence for the usefulness of culturing cell lines as spheroids in the process of understanding important cell biological phenomena.

Cell Adhesion↗

Cytostatic drug therapy in disseminated colorectal cancer.

5-FU is the best available single drug in advanced colorectal disease. After systemic administration approximately 15% of the patients achieve a short-lived objective remission. Survival is not prolonged by therapy. Several chemotherapy combinations have in preliminary phase II studies given higher response rates (30-50%), but when evaluated in controlled studies, no advantage over single-drug 5-FU has been verified. At present, two combinations, MOF-S and sequential MTX/5-FU/Leucovorin seem promising, but more experience is needed before general acceptance. In cases of liver dissemination, regional hepatic infusion therapy causes objective tumour regression more often than systemic therapy. However, median survival is most likely the same for both treatment modalities, and since hepatic artery infusion is the most expensive therapeutic modality, routine use of hepatic artery infusion is discouraged. Outside clinical trials, systemic or regional chemotherapy is hardly indicated in advanced colorectal disease apart from certain selected symptomatic patients.

Antineoplastic Agents↗

Management of epidermoid carcinoma of the anus.

In two unselected, consecutive and population-based patient materials from two regions in Sweden, different treatment modalities in patients with epidermoid carcinoma of the anus have been evaluated. By using a primary radiotherapeutic approach, combined with surgery in patients with large and/or less radiosensitive tumours, considerably more surviving patients can be disease-free in the long term compared with a primarily surgical approach. In addition, several patients will have preserved anal function. Based upon these data together with the experience described in the literature, we conclude that surgery is no longer the primary treatment of choice in patients with anal carcinoma.

Adult↗

Perioperative radiotherapy in rectal carcinoma.

Surgery alone is not sufficient for a large group of patients with adenocarcinoma of the rectum. With a combination of surgery and radiotherapy a significantly decreased local recurrence rate has been found, provided that the dose level has been sufficiently high. Whether a combined treatment has an impact on survival is too early to determine. An essential question is whether this additional treatment with irradiation should be given to all patients with rectal carcinoma, i.e. preoperatively or only to patients in Dukes' stage B or C, i.e. postoperatively. For several reasons mentioned in this paper preoperative radiotherapy is to be preferred. Furthermore, a postoperative regime is more difficult to handle within the desired schedule times. Also, data obtained in the Uppsala trial further indicate that a brief, convenient and apparently safe preoperative regime may result in a lower rate of local recurrence than an optimized postoperative regime. It is too early, however, to state that all patients with rectal carcinoma should have combined treatment. Further controlled trials, preferably with preoperative high-dose irradiation schedules, have to be carried out before the benefit of radiotherapy can be said to be conclusively proved. It is also important, however, that the surgical procedure be optimal, since irradiation cannot, and should not, serve as a substitute for poor surgery.

Adenocarcinoma↗

Preoperative serum markers in carcinoma of the rectum and rectosigmoid. I. Prediction of tumour stage.

Preoperative serum concentrations of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and a monoclonal-antibody-defined carcinoma-associated carbohydrate antigen, CA-50, were measured in 272 consecutive patients with histopathologically proven rectal carcinoma. The levels of all three tumour markers correlated directly to the stage of the disease. The serum TPA reflected both the local tumour burden and any metastatic spread, as shown by analysing mean levels of S-TPA and by the use of a Walker and Duncan regression model. S-CA-50 separated patients with and without distant metastases, but not with regard to the local tumour burden. Although the level of S-CEA correlated to the tumour stage, it did not discriminate patients with respect to locally advanced growth or generalized disease. In a multivariate analysis, the serum level of TPA was found to be the most informative preoperatively. Both S-CA-50 and S-CEA gave information additional to that provided by S-TPA in the prediction of the tumour stage (Dukes' stage A-D), and S-CA-50 was also useful in the prediction of metastatic disease.

Adult↗