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Biomedical subjects

A G Stansfeld

Publications and source records attributed to A G Stansfeld.

At least 19 recordsLinked to original sources

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy.

Adolescent

Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes).

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.

Adolescent

An immunohistological and genotypic study of the plasma cell form of Castleman's disease.

The plasma cell variant of Castleman's disease (angiofollicular hyperplasia) is an uncommon and poorly understood lymphoproliferative disorder which may be associated with a wide variety of systemic features. The clinical, pathological, immunophenotypic and genotypic features of a series of five cases are presented. The clinical manifestations were variable but systemic features were present in four cases. Histologically, all five cases were similar. The characteristic follicle-like structures are composed of concentric rings of B-lymphocytes with a mantle zone phenotype, surrounding an inner core of dendritic reticulum cells. The central regions are composed of plump cells that express Factor VIII related antigen, stain with Ulex europaeus I and are associated with laminin immunoreactivity. Many of these cells stain with Ki67 indicating cellular proliferation. Between these 'follicles', plasma cells are present interspersed between high endothelial venules. Using immunohistochemical techniques two cases were polyclonal, whilst in two others unequivocal lambda/IgA restriction was present; in the other case an intermediate picture of lambda/IgA predominance was apparent. Genotypic studies in three cases indicated immunoglobulin gene rearrangements but germ line T-cell receptor genes. The significance of the apparent clonal proliferation of plasma cells is discussed and a unifying model of Castleman's disease is proposed.

Adult

The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma.

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.

Antibodies, Monoclonal

Low field strength magnetic resonance imaging of the spleen: results from volunteers and patients with lymphoma.

Low field strength (0.08 Tesla) magnetic resonance imaging (MRI) of the spleen with spin lattice relaxation time (T1) measurement was performed on a total of 79 healthy volunteers and 62 patients with lymphoma. Inhomogeneity was observed on the T1 images of the spleen from 25 volunteers. This was therefore considered a normal variant. The normal range of spleen T1 at 0.08 Tesla was established (362-420 msec). No influence of age on spleen T1 was detected. The range of T1 values observed in males and females was similar, although the mean spleen T1 for females was significantly longer than that for males. The sensitivity of T1 measurement for the detection of lymphoma in the spleen was poor, particularly for patients with Hodgkin's disease. In a minority of untreated patients, however, a spleen T1 value outside the normal range may indicate the presence of lymphoma in the spleen. A significant decrease in spleen T1 following treatment was observed in 9 patients who underwent serial scanning.

Adolescent

A comparison of nucleolar organizer region staining and Ki-67 immunostaining in non-Hodgkin's lymphoma.

Eighty cases of non-Hodgkin's lymphomas were examined independently using the monoclonal antibody Ki-67 and an argyrophilic method for the demonstration of nucleolar organizer regions. The evidence that Ki-67 immunoreactivity may be used as a marker of cell proliferation is described and the nature of nucleolar organizer regions reviewed. The proportion of tumour cells with nuclear Ki-67 immunoreactivity and the mean number of nuclear organizer regions are shown to be linearly related (r = 0.86, P less than 0.001) although some scatter was observed. These data suggest that the mean number of nucleolar organizer regions may reflect the cellular kinetics of a tumour. This study also provides further evidence supporting the thesis that the mean nucleolar organizer region score is related to the histological grade of non-Hodgkin's lymphoma. Ki-67 immunostaining and nucleolar organizer region staining would seem to provide comparable data, at least in non-Hodgkin's lymphoma, but the latter method has the advantage of being applicable to conventionally fixed and processed paraffin sections.

Antibodies, Monoclonal

Paraffin section immunohistochemistry. I. Non-Hodgkin's lymphoma.

Reagents that recognize antigens on lymphoid cells in fixed and wax-embedded sections have been applied to a series of cases of non-Hodgkin's lymphomas. The panel consisted of MB1, 4KB5 (CD45r), LN1, L26 and MB2 which recognize antigens expressed predominantly on B-lymphocytes; UCHL1 and MT1 which recognize antigens expressed on T-lymphocytes and myeloid cells; antibodies recognizing the non-lineage antigens LeuM1 (CD15), BerH2 (CD30), anti-EMA; anti-lysozyme and MAC 387 which detect antigens present on some macrophages; and finally TAL1B5 (class II MHC), CAM 5.2 (low molecular weight cytokeratin) and PD7/26 + 2B11(CD45). Two hundred and four cases of non-Hodgkin's lymphoma have been studied, of which 158 had been fully characterized on frozen sections. The series was biased towards high-grade (n = 108) and T-cell (n = 44) tumours and these were largely prospectively accrued. It was found that discrimination between B-cell and T-cell lymphomas can be reliably achieved using these reagents and that a small panel (CD45, L26, MB2, MT1, UCHL1) is adequate for this purpose. Using the full range of reagents it is not possible to subdivide cases into groups that correspond with morphological subtypes of lymphoma. Although paraffin section immunohistochemistry is of value, the diagnosis of lymphoproliferative disorders must still be based upon the assessment of well fixed, carefully prepared tissue sections using conventional tinctorial methods.

Antibody Specificity

Paraffin section immunohistochemistry. II. Hodgkin's disease and large cell anaplastic (Ki1) lymphoma.

A panel of antibodies that recognize antigens that survive fixation and conventional processing have been applied to 43 cases of Hodgkin's disease and five cases of large cell anaplastic lymphoma. Reed-Sternberg cells in all five cases of nodular lymphocyte predominance Hodgkin's disease were positive with leucocyte common (CD45) and B-cell antibodies, and negative with LeuM1 (CD15) and BerH2 (CD30) antibodies. In other types of Hodgkin's disease, Reed-Sternberg cells were positive with BerH2 in all cases, positive with LeuM1 in 63% of cases (with enzymic predigestion), positive with at least one B-cell antibody in 29% of cases and positive for CD45 in 8% of cases. In 19% of all cases, Reed-Sternberg cells were positive for epithelial membrane antigen and in 93% they were positive with TAL1B5 (anti-class II MHC). No case showed immunoreactivity with anti-T-cell antibodies. The patterns of immunoreactivity of large cell anaplastic lymphoma were similar, except that none was positive with B-cell antibodies and three were positive with T-cell antibodies. All five were positive with BerH2 (CD30) and TAL1B5. Comparison of the results with those seen in other cases of non-Hodgkin's lymphoma indicates that, with the currently available reagents, this immunohistological profile cannot be used as the sole diagnostic discriminant of these conditions; this must still be based upon careful morphological assessment.

Antigens, Surface