In vivo labelling of human tumours with bromodeoxyuridine: a histopathologist's view.
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Bromodeoxyuridine↗
Biomedical subjects
M H Bennett
Publications and source records attributed to M H Bennett.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Acute thyroid crisis on induction of anaesthesia.
Thyroid crisis on induction of anaesthesia was treated with dantrolene, because of a mistaken diagnosis of malignant hyperthermia. There was immediate improvement after dantrolene with reduction in muscle rigidity, mental confusion and pyrexia. High circulating T4 has an effect on calcium flux across the sarcoplasmic reticulum and dantrolene may inhibit this pathological mechanism. We suggest the same dosage regimen as is used in the treatment of malignant hyperthermia.
Acute Disease↗
Lymphoplasmacytoid lymphoma elaborating lambda chain paraprotein with amyloid deposition in Sjögren's syndrome.
A woman presented with painful enlargement of her parotid and submandibular glands. She was shown to have the previously unreported combination of idiopathic thrombocytopenic purpura, Sjögren's syndrome, Hashimoto's disease, and myasthenia gravis. Parotid gland biopsy and bone marrow examination showed the presence of a rare lymphoplasmacytoid lymphoma. There was amyloid deposition in the parotid glands, gums and on muscle biopsy. Immunohistochemical staining of the parotid lymphoma and amyloid was monotypic for lambda light chains, and there was also a lambda chain paraprotein. It is felt that the lymphoplasmacytic lymphoma was responsible for the light chain amyloidosis.
Adult↗
Evoked-potential monitoring during dorsal root entry zone surgery. Patients with chronic pain.
Somatosensory evoked potentials (SEP) were monitored intraoperatively in 15 patients who underwent spinal cord radiofrequency thermal dorsal root entry zone (DREZ) lesion procedures to treat chronic deafferentation pain. We found a significant correlation between transient latency shifts (recovery to prelesion values in the postlesioning period) of the first positive peak of the SEP (P1) during lesion production and the patients' subsequent postoperative neurological status (p less than 0.01). Transient increases in P1 latency above 2 ms were associated with detectable but transient postoperative sensorimotor deficits that resolved weeks to months after surgery. In 1 patient, the intraoperative P1 latency failed to return to baseline values; this patient had irreversible postoperative sensorimotor dysfunction. In 9 patients, we confirmed the value of recording bilateral SEP, using the contralateral side of the spinal cord (with no lesions) as a control. This experience has resulted in an improved SEP monitoring strategy: we now reconsider the risk-benefit ratio of additional DREZ lesions if early lesion production results in increased P1 latency. Rapid normalization of the P1 latency indicates that any postoperative deficits likely will resolve. Failure of P1 latency to return to control levels during the surgical wound closure period (approximately 1 h) indicates the high probability of permanent neurological deficits.
Electrocoagulation↗
Evoked-potential monitoring during dorsal root entry zone surgery. An experimental animal model.
Spinal cord evoked potentials (SCEP) in response to epispinal stimulation were measured in an experimental animal model designed to define further the value of electrophysiological monitoring during dorsal root entry zone (DREZ) surgery. Thirteen cats underwent microsurgical stereotactic thermal radiofrequency lesions of the DREZ. The postmortem histological examination of the location and extent of the lesions were compared with the intraoperative electrophysiological and postoperative neurological effects. Despite the use of the stereotactic microsurgical technique, the sizes and the configurations of the DREZ lesions varied greatly. Changes in ascending and descending SCEP correlated highly with the extent of the histologically defined injury to the dorsal and lateral columns. SCEP monitoring during experimental DREZ surgery provided a sensitive indication of lesion invasion into the dorsal or lateral columns. The high degree of correlation between changes in descending SCEP and extension of the surgical lesion into the lateral column indicates that the SCEP technique is more sensitive than somatosensory cortical evoked potentials in the intraoperative electrophysiological assessment of corticospinal tract function, and it may prove to be a useful surgical adjunct during DREZ surgery in humans.
Animals↗
Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry.
The proliferative potential of human solid tumours, in vivo, was investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Patients with solid tumours from a variety of sites were injected with 500 mg BrdUrd, intravenously, several hours prior to biopsy or surgical excision. The labelling index (LI), duration of S-phase (Ts) and thus the potential doubling time (Tpot) could be measured within 24 h of sampling. The results show that both the LI and Ts vary greatly between tumours (Ts ranges from 5.8 to 30.7 h). However, within this study of 26 evaluable patients, tumours of the same tissue origin tended to have similar Ts values. Melanomas had the shortest Ts (8.8 h), nine patients with head and neck cancer had Ts values ranging from 5.8 to 18.8 h (median 12.5 h). The longest Ts values (24 h) were found in lung and rectum. The estimates of Tpot ranged from only 3.2 days in an oat cell carcinoma to 23.2 days in a lymphoma. The striking feature of the study was that 38% of the tumours had a potential doubling time of 5 days or less. We found no relationship between proliferation and histopathological differentiation or DNA ploidy. It should now be possible to assess the prognostic significance of pretreatment cell kinetic measurements which may, in the future, aid in the selection of treatment schedules for the individual patient.
Bromodeoxyuridine↗
Malignant lymphoma presenting as an ovarian tumour: a clinicopathological analysis of 34 cases.
The clinicopathological features of 34 patients with malignant lymphoma or leukaemia where the initial presentation was as an ovarian tumour are described. Nineteen patients died, usually within 1 year of diagnosis, whilst 15 survived, some for long periods. Factors indicating a poor prognosis were rapid onset of abdominal symptoms, the presence of systemic symptoms, bilateral ovarian tumours, advanced stage and a histological pattern other than that of a B-cell lymphoma. For staging purposes the Ann Arbor method appeared a more sensitive prognostic indicator than did the FIGO staging system. It is suggested that primary malignant lymphomas of the ovary are extremely rare and that for therapeutic purposes all lymphomas of the ovary should be regarded as local manifestations of systemic disease.
Acute Disease↗
Primary non-Hodgkin's lymphoma of the orbit.
Between 1954 and 1980, 9 patients with non-Hodgkin's lymphoma of the orbit were treated at the Regional Radiotherapy Centre, Mount Vernon Hospital. Following radiotherapy complete local regression of the tumour was seen in every case. Three patients subsequently developed recurrent disease which proved fatal in two cases. The overall 5 year survival was 89%.
Adult↗