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Biomedical subjects

M H Bennett

Publications and source records attributed to M H Bennett.

At least 19 recordsLinked to original sources
PubMed1994

The significance of MALT histology in thyroid lymphoma: a review of patients from the BNLI and Royal Marsden Hospital.

Data from a series of 45 patients with Stage I and II non-Hodgkin's lymphoma (NHL) of the thyroid gland were analysed retrospectively to determine the incidence and prognostic significance of histopathological features of tumour origin from mucosa associated lymphoid tissue (MALT). The overall 5- and 10-year cause specific survival from NHL for the series was 79%. Evidence of tumour origin from MALT was the only significant prognostic factor for overall survival identified by multivariate analysis of the series (P < 0.01). A total of 31 (69%) tumours showed such evidence, the cause specific patient survival from NHL at 5 and 10 years being 90% compared with only 55% at 5 years for the 14 patients without such evidence. For patients given initial treatment with radiotherapy alone, those with evidence of tumour origin from MALT had a relatively low relapse rate and a relatively high success rate from salvage therapy, compared with a relatively high relapse rate and negligible success from salvage therapy in those without evidence of such tumour origin.

Adolescent↗
PubMed1993

Non-Hodgkin's lymphoma of the testis.

Primary non-Hodgkin's lymphoma of the testis is rare. From 1976 to 1989 32 patients have been registered with the British National Lymphoma Investigation and two with the Institute of Urology. All 34 patients had disease of high grade histology (BNLI) although in four patients there were some areas with features similar to those described in lymphomas of Mucosal Associated Lymphoid Tissue (MALT). Twenty-three of 34 (67.5%) patients had early stage disease (I/II); 17/34 (50%) achieved complete remission from their initial treatment, and the relapse-free survival of these patients was 66% at 5 years. The disease-free survival for the 34 patients as a whole was 33% and their overall survival 39% at 5 years. The life expectancy for those presenting with advanced (stage III/IV) disease was very poor (median survival 9 months) with a low complete remission rate from chemotherapy. The salvage rate from recurrent disease (17%) was poor. Bilateral testicular involvement (18%) and a high rate of central nervous system disease (21%) occurred in the series, and two patients were HIV positive. Stage at presentation was the most important prognostic factor.

Adult↗
PubMed1993

Primary gastrointestinal non-Hodgkin's lymphoma: a review of 175 British National Lymphoma Investigation cases.

A retrospective analysis was performed upon 175 patients with Non-Hodgkin's Lymphoma involving the gastrointestinal tract and entered into BNLI trials and studies between 1974-1988. Malignant histiocytosis of the intestine (MHI), which was present in 16 patients, was associated with a survival of less than 25% at 18 months, and probably accounted for the poor survival of patients with jejunal involvement. Histopathological evidence of tumour origin from mucosa-associated lymphoid tissue (MALT) was found in 50% of patients with gastric involvement and in 27% of those with intestinal involvement. The overall survival of the series as a whole was 44% at 10 years. Multivariate analysis identified evidence of tumour origin from MALT as the only factor to attain prognostic significance in patients with gastric involvement, and clinical stage and the presence of MHI as the only factors to attain prognostic significance in patients with intestinal involvement. It is suggested that there is a need for a large multicentre prospective study of GIT lymphoma.

Adolescent↗
PubMed1992

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE: To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin's disease. DESIGN: Cohort study. SETTING: The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS: 2846 patients first treated for Hodgkin's disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES: Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin's disease and of second primary non-Hodgkin's lymphomas. RESULTS: 113 second primary cancers occurred. Relative risk of cancer other than Hodgkin's disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin's lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin's lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION: The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin's disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin's disease.

Adolescent↗
PubMed1992

Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck.

The two techniques of flow cytometry analysis (FCM) and immunohistochemical localisation of bromodeoxyuridine (BrdUrd) incorporation after in vivo administration, were combined to study proliferation in squamous cell carcinoma of the head and neck region. Care was taken in this study to ensure that similar material was processed using both techniques such that comparisons could be made. FCM underestimated the labelling index (LI) in tumours classified as diploid compared to the histological evaluation of the tumour cells within those tumours (4.6% vs 17.1%). However, in aneuploid tumours, the FCM LI (10.7%) was similar to that obtained from histology (13.5%). Indeed, proliferation assessed by the combination of histology LI and FCM duration of S-phase (Ts) indicated that diploid tumours had a shorter median potential doubling time (Tpot) of 2.1 days compared to aneuploid (2.8 days). Despite the heterogeneity of proliferation evident histologically within the specimens, there was not a wide variation in the results of FCM analysis when multiple samples from resections were studied. Using FCM data alone, 46% of the tumours showed a Tpot of less than 5 days. When the Ts from the FCM data was combined with the average histological LI, 84% were less than 5 days and with the maximum LI, 99% were within this time interval. Compared with previous estimates, the proportion of tumours possessing proliferative characteristics which may indicate the need for acceleration of treatment seems to be much larger.

Aneuploidy↗
PubMed1992

LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial.

PURPOSE: The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS: Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS: The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse-free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION: These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1991

Flow cytometric study of nodular fasciitis, proliferative fasciitis, and proliferative myositis.

DNA ploidy was assessed retrospectively, using flow cytometry, in 13 nodular fasciitis (NF) lesions, three proliferative myositis (PM) lesions, one proliferative fasciitis lesion, and 12 other benign fibrous lesions (BFLs). All were diploid. In view of the large amounts of cellular debris, cell cycle analysis was possible in only seven NF lesions, three PM lesions, and six BFLs. The mean percentage of S phase did not differ markedly between the combination of NF and PM lesions (6.6%) and BFLs (7.1%); the mean percentage of G2 + M phase (5.4%) of the NF/PM lesion combination was twice as large as that of the BFLs (2.5%). No correlation was detected between the cell cycle analysis and the mitotic count, the predominant histologic type in NF lesions, or the predominant stroma in PM lesions.

DNA↗
PubMed1991

Kikuchi's necrotising lymphadenitis.

Three cases of Kikuchi's necrotizing lymphadenitis without granulocytic infiltration presented to the ENT department as cervical lymphadenopathy with neutropaenia. Differential diagnosis from malignant lymphoma was difficult both clinically and histopathologically. Two recovered spontaneously without treatment within three months, one improved initially but was lost to follow-up after one month.

Adult↗
PubMed1991

British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results.

From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkin's disease; there were no infective deaths in the absence of Hodgkin's disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkin's lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkin's disease.

Adolescent↗
PubMed1991

Non-Hodgkin's lymphoma arising in patients treated for Hodgkin's disease in the BNLI: a 20-year experience. British National Lymphoma Investigation.

Twenty-two of 3033 patients with Hodgkin's disease (HD) randomised into the clinical trials of the BNLI have developed non-Hodgkin's lymphomas (NHLs) at periods up to 16 years after presentation (1 simultaneous and 1 composite), giving an incidence of 0.7%. The frequency of NHL varied from 3.8% in lymphocyte-predominant HD to 0.3% in nodular sclerosing HD. In this series, 16 patients developed high-grade NHL (12 B cell; 4 peripheral T cell) and 6 developed low-grade NHL (all B cell). The histological subtype of NHL did not appear to be related to initial histological subtype of HD or the treatment received. In histological subtypes other than lymphocyte predominant, there was commonly evidence of immunosuppression in the form of low presentation lymphocyte counts, advanced stage and systemic (B) symptoms. The results suggest that these patients have a propensity for lymphoproliferative disorders, possibly associated with some immune deficiency and the subsequent development of NHL is not treatment related. The findings also emphasise how important it is to biopsy recurrent disease.

Adult↗
PubMed1991

Proliferative myositis. An immunohistochemical and ultrastructural study.

We studied four cases of proliferative myositis by the avidin-biotin-peroxidase complex technique, using a panel of 12 antibodies, and by electron microscopy. The aim was to clarify the nature of their constituent cells, specifically the giant ganglion-like cells and spindle cells, and to discuss the implications for histogenesis. In all cases, both cell types showed positive cytoplasmic staining with antibodies to vimentin, actin (C4), and alpha-smooth muscle actin-1, but in only one was there positive staining with desmin. No staining was obtained with factor XIIIa, muramidase, alpha-1-antitrypsin, myoglobin, S-100 protein, CAM 5.2, factor VIII-related antigen, or neuron-specific enolase. By electron microscopy, both types of cells were seen to contain numerous thin filaments, dense bodies, coated and pinocytotic vesicles, active and dilated rough endoplasmic reticulum, few microvilli, and incomplete desmosomal junctions. Our findings imply a myofibroblastic nature for the giant ganglion-like cells and spindle cells. Our observations also support the hypothesis that they are derived from a pericytic cell.

Actins↗
PubMed1989

Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease. A study of 1659 patients.

Nodular sclerosing (NS) Hodgkin's disease (HD) with extensive areas of lymphocyte depletion or with numerous anaplastic Hodgkin's cells, termed Grade II NS, is associated with a poor response to initial therapy, an increased relapse rate, and decreased survival when compared with other NS variants, termed Grade I NS. The histopathologic subdivision of NS HD into Grade I and Grade II is easy to perform and provides essential prognostic information that is independent of stage. Patients with Grade II NS HD may require more aggressive initial therapy if their survival is to be improved.

Adolescent↗
PubMed1989

Cell proliferation and differentiation in squamous cancer.

Cellular differentiation is generally regarded as an important histological predictor of tumour behaviour. Verrucous carcinoma is a very well-differentiated tumour characterised by slow enlargement and an unsatisfactory response to radiotherapy. Tumour cell kinetic studies using the intravenous administration of bromodeoxyuridine (BrdUrd) before tumour sampling have shown these tumours to have high labelling indices and short duration of DNA synthesis. These values result in short potential cell doubling times of these tumours although they then have a well-differentiated appearance histologically. Study of 20 other squamous cell carcinomas has shown no relationship between grade and cell proliferation.

Bromodeoxyuridine↗
PubMed1989

The uptake of the radiosensitizing compound Ro 03-8799 (Pimonidazole) in human tumors.

The nitroimidazole, Ro 03-8799, has proved unique among the drugs tested as chemical hypoxic cell radiosensitizers because of the preferential concentration which has been observed in tumors. Our accumulation of experience has allowed new analyses to be performed upon 127 samples from 39 patients; 47 samples of normal tissue were also obtained from 26 of these patients. Tissue sampling was performed usually between 20 and 30 minutes after initiation of infusion of Ro 03-8799. By expressing results as tumor: plasma ratios, difficulties in comparison because of differing doses and body sizes, together with a variation in the actual time of sampling, have been avoided. A small portion of each specimen which was analyzed for drug concentration was also examined histologically to give an impression of the percentage of the specimen occupied by tumor cells. Analyses have shown that the average tumor concentration is approximately twice that of normal tissues which have been sampled and four times that in plasma. In 38 breast tumor samples, the concentration of drug varied directly as the proportion occupied by tumor cells. The highest tumor: plasma ratios were seen in samples taken from some samples of malignant melanoma. These findings confirm that a greater potency can be expected for this drug as a radiosensitizer because of its ability to enter tumor cells in high concentration. In drug development programs for chemical sensitizing and cytotoxic agents, drugs which show this phenomenon should be explored.

Breast Neoplasms↗
PubMed1989

Non-Hodgkin's lymphoma of the nasopharynx, paranasal sinus and palate.

Twenty-two patients with non-Hodgkin's lymphoma of the nasopharynx, paranasal sinuses or palate were treated between 1952 and 1980. The histology was reviewed by one histopathologist and 77% of cases were classified as grade 2 non-Hodgkin's lymphoma. Forty-five per cent of patients relapsed after initial treatment and 41% of all patients died from lymphoma. The 5-year survival ranged from 22% for the nasopharynx to 80% for the palate.

Adolescent↗
PubMed1989

The prognostic influence of mediastinal bulk in pathological stage IIA Hodgkin's disease treated initially with radiotherapy.

The response to treatment and survival has been assessed in 61 patients with pathological Stage IIA Hodgkin's disease with mediastinal involvement who were treated initially by supradiaphragmatic radiotherapy alone. Although 57 (93%) obtained complete remission, 29 have relapsed giving a total of 33 (54%) treatment failures. The percentage of patients actuarially disease free at 5 years is 44% although overall survival is 90%. The "bulk" of the mediastinal disease was assessed on a plain chest X-ray by measurement of the widest diameter of the mass compared to thoracic diameters at various levels as well as by determination of the area of the mass. The ratio of the widest diameter of the mass to the widest internal thoracic diameter provided the greatest prognostic information. Patients with a ratio greater than 0.33 (30% of total) had an actuarial disease-free survival of 24% at 5 years compared to 54% in patients with smaller mediastinal masses (P less than 0.05). Mediastinal bulk was not correlated with histological grade. Patients with the largest mediastinal masses (ratio greater than 0.37) (10% of total) have a lesser survival, but in the remainder, measurement of the mediastinal mass did not predict survival, indicative of the excellent salvage rate with subsequent chemotherapy. The implication of these findings for the treatment of stage IIA Hodgkin's disease with mediastinal involvement is discussed.

Adolescent↗