[Screening of cancer in ulcerative colitis--unnecessary surgery should be avoided].
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Biomedical subjects
Publications and source records attributed to A Ost.
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Dysplastic features of peripheral blood granulocytes were studied to investigate the diagnostic value estimating cytoplasmatic hypogranulation and nuclear abnormalities of the pelgeroid type in myelodysplastic syndromes (MDS). Hypogranulation was measure both as the percentage of agranular neutrophils and as a score value, taking into account also cells with slight or moderate hypogranulation. We studied 62 cases of MDS (18 refractory anemia, 11 sideroblastic anemia, 26 refractory anemia with excess of blasts, three chronic myelomonocytic leukemias, four refractory anemia with excess of blasts in transformation). For comparison we studied 13 cases of myeloproliferative disorders, 18 patients with different forms of anemia and 20 normal controls. Reference values were defined as the 95% probability limit of the mean values of normal controls. In MDS 52/62 patients (84%) had increased numbers of pelgeroid cells, 40/62 (65%) had abnormal granulation scores while only 14/62 (23%) had increased percentages of agranular neutrophils. The mean granulation score (+/- S.D.) in MDS (225.0 +/- 57.4), was significantly lower (p less than 0.001) than in myeloproliferative disorders (282.7 +/- 9.0), anemias (288.8 +/- 8.0) and normal controls (281.7 +/- 12.9). Pelgeroid neutrophils were significantly (p less than 0.001) more common in MDS (11.6% +/- 7.8) compared to myeloproliferative disorders (1.1% +/- 1.0), anemias (3.1% +/- 2.0) and normal controls (1.9% +/- 1.5). There was no significant correlation between the degree of hypogranulation and the percentages of pelgeroid cells in individual patients. Hypogranulation tended to be more pronounced in the more immature forms of MDS while pelgeroid cells were equally common in the different subgroups. When the two parameters were combined peripheral blood dysplasia was recognized in 92% of the MDS cases. The results suggest that quantitative estimation of hypogranulation and of nuclear abnormalities in peripheral blood polymorphs are simple and valuable diagnostic tools in MDS.
Bone marrow cells from 15 patients with myelodysplastic syndromes and 2 with acute myeloid leukemia were incubated in vitro with all-trans-retinoic acid (RA), 1,25-dihydroxy vitamin D3 (D3), cytosine arabinoside (ara-C) and alpha-interferon (IFN). 3H-thymidine incorporation (3H-TdR), differentiation and clonal growth were studied. D3 was found to be the most effective inducer of differentiation and differentiation was correlated with a decreased 3H-TdR. Differentiation with one of the inducers was significantly correlated to differentiation with any of the other inducers. Patterns of differentiation and spontaneous and D3-induced 3H-TdR were used to divide the patients into 3 different groups. In the first group, 5 patients with extremely low spontaneous 3H-TdR and differentiation in combination with a slightly increased 3H-TdR after induction differed from all other patients by a higher percentage of bone marrow blast and a more pronounced pancytopenia. The two other groups had a high spontaneous 3H-TdR but differed with respect to the D3-induced differentiation which was absent in one group (n = 6) and present in the other (n = 5). The two groups showed no difference in the clinical features.
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In seven patients with longstanding ulcerative colitis, multiple mucosal biopsies taken at colonoscopy were assessed for DNA content and histological dysplasia. DNA analyses were performed using flow cytometric analyses in biopsies and microspectrophotometry in imprint slides prepared from the biopsies. Abnormal aneuploid DNA content was detected in five of the patients in eight separate locations in the colon. There was good conformity between the two methods in the detection of aneuploidy. Both methods of DNA analysis are considered to be applicable in mucosal biopsies from patients with ulcerative colitis. In two patients with significant low grade dysplasia in association with macroscopical lesions (DALMs), there was a relationship with aneuploid DNA pattern found by flow cytometric or microspectrophotometric analyses. Indefinite changes, probably dysplastic were found in three other patients and two of those also displayed aneuploidy, although only once in the same biopsy location. In five locations aneuploidy was detected without concomitant dysplasia. DNA-aneuploidy seems therefore to appear earlier than dysplasia and may be an early marker of malignant transformation of the mucosa in ulcerative colitis. Prospective trials are needed before the clinical significance of early findings of aneuploidy can be determined.
Current treatment strategies in northern Europe of non-Hodgkin lymphoma are presented. High-grade malignant lymphomas have been treated with doxorubicin-containing polychemotherapy in various modes. The advantage of six-drug regimens over CHOP-like therapy is as yet not proven. Patients with the ability to tolerate the calculated dose have good prognosis. High-dose therapy and bone marrow transplantation should be considered in poor-risk patients with lymphoblastic lymphomas in first remission, patients with all high-grade histologies in partial remission after first-line therapy and patients with relapse that are still responsive to therapy. Preliminary results from autologous bone marrow transplantation in follicular lymphoma are also encouraging. Chlorambucil induces multiple remissions in follicular lymphoma, with a median duration of the 1st, 2nd and 3rd remission being the same. The watch and wait strategy seems justified initially in most asymptomatic generalized low-grade malignant lymphomas. Systemic therapy is required in aggressive stage II-IV lymphomas. A meticulous investigation is needed for stage I patients before giving local treatment only. Immune phenotyping is of great value for diagnosis and staging. Liver, but not bone marrow involvement seems to be an adverse prognostic factor. Follicular lymphoma is an example of a dynamic tumour with gradual cellular changes associated with new and more malignant clinical signs.
The histological alterations seen in HIV-related lymphadenopathy have been described with different terms by different authors. In order to facilitate comparisons of results from various laboratories, a group of pathologists of the European Lymphoma Study Group (later the European Association for Haematopathology) have proposed a histological classification for the evaluation of HIV related lymphadenopathy. Most observers agree that the morphological and immunohistochemical alterations in the follicles (germinal centres) are the most conspicuous and earliest changes seen. The follicular alterations were therefore used as the basis for the proposed classification. In addition, some features occasionally seen were also included, i.e. angioimmunoblastic hyperplasia, multicentric Castleman-like lesions, and vascular lesions, especially pretumorous and tumorous stages of Kaposi's sarcoma. The proposed classification was used by the members of the group of a collection of lymph nodes compiled from the various centres. The classification was shown to be reproducible and to have clinical relevance in staging of the patients. The prognostic relevance as to the survival of the patients has to be further substantiated by follow-up studies. The proposed classification offers a common terminology for the alterations previously described by different terms by various authors.
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A large number of lymphocytes each surrounded by a clear halo were found in the foveolar epithelium of the fundic region and the antrum in a gastric biopsy from a patient with epigastric complaints. Electron microscopical studies demonstrated the presence of intraepithelial "in-halo" lymphocytes both underneath, between two contiguous, and within foveolar gastric cells. Normal numbers of lymphocytes (without haloes) were found in the lamina propria, suggesting that this epithelial lymphocytosis may be unrelated to "classical" chronic gastritis. The possibility of an autoimmune phenomenon at the foveolar cell level was discussed. The absence of intraepithelial lymphocytes in the glandular epithelium suggests that this phenomenon may be unrelated to the type of autoimmunity found in pernicious anaemia.
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Fifty-nine lymph node biopsies from homosexual men with serum antibodies to HTLV-III/LAV were the subject of a detailed histopathological and immunohistochemical study. The histological findings were correlated to the patients clinical status, and the T4/T8 ratios in blood and lymph nodes. Four histological patterns predominated and were defined as follicular hyperplasia (FH), follicular fragmentation (FF), follicular atrophy (FA), and follicular depletion (FD). Immunocytochemical studies indicated that destruction of follicular dendritic cells is related to the initiation of follicular involution from FH to FF, but the possible role of follicular infiltrating T-cells cannot be excluded. Marked individual variations in lymph node angiogenesis increasing during involution were observed, which suggests that the degree of angiogenic host response may predispose for evolution of Kaposi's sarcoma. The majority of the patients with the clinical diagnosis of persistent generalized lymphadenopathy (PGL) were morphologically staged as FH or FF (89%), whereas most of the AIDS patients showed lymph node changes compatible with FA and FD (89%). Patients with AIDS-related complex (ARC) had a wider spectrum of morphological lymph node changes but a majority of cases (62%) were also classified as FA or FD. Clinical follow-up showed progression from PGL to ARC in seven of 21 cases with the FF pattern and only in three of 19 cases with FH, indicating a possible prognostic value in differentiating between FH and FF. Three cases with FD and one with FA progressed to AIDS during the time of observation. T4/T8 ratios in blood and lymph nodes were significantly lower in patients with FD histology compared to patients of the other histological groups. At autopsy, all AIDS cases showed the FD pattern of lymphadenopathy. Autopsy findings in seven patients emphasized the importance of post-mortem studies in clarifying the spectrum of opportunistic diseases, including tumors which afflict the AIDS patients.
During a prospective study lasting 3.5 years flow cytometric DNA analysis was evaluated as a possible predictor of dysplastic and malignant lesions in longstanding ulcerative colitis. Fifty three patients with total ulcerative colitis (mean disease duration of 22 years) were regularly colonoscoped. Biopsies of colonic mucosa were analysed by flow cytometric technique and were also assessed histologically. Findings of abnormal DNA pattern (aneuploidy) were compared with findings of dysplasia. Five patients (9%) had aneuploidy, four of those at repeated colonoscopies. Four of those patients also had various degrees of dysplasia. In one patient aneuploidy preceded the finding of dysplasia and in another aneuploidy preceded a well differentiated adenocarcinoma, grade Dukes' A subsequently found at surgery. Four additional patients had dysplasia, all in connection with macroscopic lesions, but were diploid. It is suggested that flow cytometric DNA analysis in long standing ulcerative colitis may be helpful in addition to histopathology in the detection of potential malignancy in ulcerative colitis.
Patients with a definite diagnosis of ulcerative colitis in Stockholm County during the 35-year period 1945-79 were identified and followed up with regard to the development of cancer of the colon. We found 25 patients who had developed 31 cancers. In 24 of 25 cases this occurred in patients with total colitis. The cumulative risk of developing cancer for patients with total colitis at follow-up study was calculated by means of life-table methods. It was 13% at 25 years (SD +/- 4.2%) among patients diagnosed in 1945-79, compared with the 1.9% expected in a population matched for age and sex. Among patients diagnosed in 1955-79 the risk was approximately 5% at 20 years (SD +/- 3.0%), compared with 1.4% for the background population. The cancer risk for all patients with colitis was higher but not significantly higher than that of the general population. The outcome of patients who developed cancer was dependent on histologic staging (Dukes's) at surgery but not on age at cancer diagnosis.
The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.
The immunological phenotypes of leukemia cell samples from 60 patients, of whom 54 had acute myeloid leukemia (AML), were assessed with a panel of monoclonal antibodies (Mabs) with specificity for the following epitopes: Epitopes associated with myeloid leukemia cells, Epitopes expressed only on immature myeloid cells (or subsets) and on monocytes, Epitopes only expressed on granulocytes or on granulocytes and mature myeloid cells (promyelocytes, myelocytes and monocytes), Epitopes on HLA-class II (DR) and HLA-class I molecules and on insulin receptors. This panel of Mabs proved useful to identify leukemia cells in blood and to assess their myeloid origin. The panel of Mabs was found also to be useful for immunophenotyping of leukemia cells. Furthermore, the analysis revealed considerable variations in the immunological phenotype of AML cells, reflecting antigenic heterogeneity within the individual leukemia cell population as well as abnormal or no expression of histocompatibility antigens and insulin receptors in some samples. Some of the Mabs bound preferentially to subgroups in the French-American-British (FAB) classification.
The levels of TdT, AdA, 5'-N, 20 alpha-SDH and TK1 were analyzed in different FAB subgroups of AML. AdA, 5'-N, 20 alpha-SDH and TK1 showed large variations both within and between the different subgroups. It therefore seems unlikely that measurements of these enzymes will be able to aid morphological subclassification of AML. Neither could analysis of these enzymes give prognostic information. TdT was detectable in 46% of AML but the levels were only 1/10-1/100 of those found in ALL. The enzyme was detected in leukaemic granulocytopoietic cells while leukaemic cells of monocytic origin were negative in all but 1 case. In addition, increased TdT activity was positively correlated to the length of survival.
An eight year endoscopical and histological cancer surveillance programme comprising 71 patients with ulcerative colitis is presented. Forty one patients had total colitis and 30 substantial colitis. Mean duration of the disease was 19.7 years (range 9-46 years). An average of 2.6 colonoscopies per patient in the total colitis group were carried out, and at least two biopsies were taken at 10 locations in the colon. In the total colitis group, seven had either low (four), or high grade dysplasia (two), or Dukes' A cancer (one). In the group with substantial colitis two patients with low grade dysplasia were found. Dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having had total colitis for 25 to 44 years. The dysplasia and cancer findings at the colonoscopy preceding surgery corresponded well with the surgical specimens. In three operated patients a sequence of dysplasia development was recorded. With the exception of long duration and dysplasia, nothing in the clinical course distinguished the operated cases. Using this surveillance programme prophylactic colectomy can be limited to patients in a high risk group developing dysplasia. The risk of missing a cancer before it becomes incurable seems to be low.
A case of gastric carcinoid tumor in a patient with pernicious anemia is presented. From a pathophysiological point of view, the treatment of choice, i.e. endoscopic removal or gastric resection, is discussed.