The gestational trophoblastic diseases: a review of their presentation and management.
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Antineoplastic Agents↗
Biomedical subjects
M S Dorreen
Publications and source records attributed to M S Dorreen.
Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants.
In this study we evaluated the clinical response of 12 patients with malignant melanoma and renal cell carcinoma (RCC) following administration of recombinant human interleukin-2 (rhIL-2) by continuous infusion. Serum samples taken before, during and following sequential courses of IL-2 were assayed for the presence of tumour necrosis factor alpha (TNF-alpha) IL-1 alpha, IL-6 and interferon gamma (IFN-gamma) and the presence or changes in these cytokines were examined with respect to clinical response data: our results did not show any direct correlation between the parameters measured and clinical outcome. In addition, peripheral blood mononuclear cells (PBMC) derived from 3 RCC patients were cultured in a serum-free environment and the resulting supernatants assayed for the production of these cytokines and compared to the corresponding serum levels. During one or more courses of treatment only 1 patient, who had metastatic bone disease, demonstrated detectable serum TNF-alpha; serum IL-6 levels were elevated in a proportion of all patients studied and a sustained IL-6 response occurred in a patient who had complete disease remission; IL-1 alpha was detected in the serum of 3 RCC patients; IFN-gamma could not be detected in any serum sample tested. Cytokine levels in sera and supernatants derived from 3 RCC patients were compared but no correlation was found: TNF-alpha and IL-6 were shown to be present at much higher concentrations in supernatants when compared to sera whereas the levels of IL-1 alpha were almost undetectable. This lack of correlation is probably due to the presence of "interfering" proteins in sera which either depress or enhance the ability to detect cytokines in sera using enzyme immunoassays.
Carcinoma, Renal Cell↗
Stage I seminoma of the testis: is post-orchidectomy surveillance a safe alternative to routine postoperative radiotherapy?
Experience with the management of 128 patients with Stage I testicular seminoma over a 10-year period, 1980-1989, is presented. Fifty-six patients were treated with post-orchidectomy radiation therapy and 72 patients were put on surveillance. Patients thought to be at higher risk of relapse were generally treated with radiotherapy. There have been no tumour related deaths in this series; 5.4% of the irradiated group and 18% of patients on surveillance have relapsed to date. All relapses have been salvaged with further therapy and are currently in complete remission. In this interim analysis, surveillance appears to be a safe alternative to adjuvant radiation therapy provided regular, prolonged follow-up can be ensured. Surveillance is, however, time consuming and resource demanding, and should be undertaken only as part of a formal clinical study. Adjuvant post-orchidectomy radiotherapy should be considered the treatment of choice until further long-term data are available.
Adult↗
Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.
The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.
Aged↗
Results of low-dose methotrexate treatment of persistent gestational trophoblastic disease in Sheffield 1980-1987.
Between January 1980 and October 1987, 115 evaluable patients were treated in Sheffield for persistent gestational trophoblastic disease (GTD) with a low dose methotrexate regimen (LD-MTX). Each course comprised MTX 50 mg given by i.m. injection for 4 doses on alternate days. Courses were repeated every 2 weeks and serum beta-hCG was used to monitor response. Overall, 80/115 (70%) of patients attained durable complete remissions (CR). Twenty-nine patients received the 'AVC' salvage combination of actinomycin-D 0.5 mg i.v. for 5 days, sequenced with cyclophosphamide 500 mg i.v. and vincristine 1 mg i.v., both given for 3 doses on alternate days. Sixteen (55%) patients attained a durable CR but 11 (38%) required further measures, 7 ultimately requiring hysterectomy. Two (7%) died during treatment. With 4 deaths overall (3 from metastatic GTD and 1 from infarction of the bowel), actuarial survival is 94% at over 7.5 years. A new Charing Cross prognostic scale weighted especially for hCG levels, number and sites of metastases, interval between pregnancy and start of treatment (score 0-6 each factor), was applied retrospectively to obtain a total score for each patient. Thus, 21/26 (81%) patients who scored greater than 8, required additional treatment after LD-MTX, compared with 18/89 (20%) of lower scoring patients (p less than 0.001). Because of the frequent morbidity associated with prolonged chemotherapy as well as the development of drug-resistant GTD, it is concluded that the 'high-risk' patients should receive more intensive combination chemotherapy at the outset.
Adult↗
Primary intracerebral lymphoma: a clinicopathological analysis of 14 patients presenting over a 10-year period in Sheffield.
Intracerebral disease was diagnosed in 14 out of 450 patients who presented with non-Hodgkin's lymphoma between January 1976 and January 1987. Twelve of the 14 presented after June 1980. Age ranged from 31 to 73 years and eight patients were male. Two patients had other tumours, and three had relevant associated immunosuppressive disorders. Radiological assessment of one further patient showed a cavitating bronchial carcinoma. Five patients were untreated, and one died before radiotherapy was complete. Eight patients completed courses of whole-brain irradiation; four of these received higher doses. All entered remission. Three patients are alive, between eight months and seven years after treatment. Of the remaining five, one never recovered intellectual function and died of bronchopneumonia; three died between eight and 30 months after treatment and autopsy showed severe radionecrosis of the brain with no residual tumour. All three had received higher doses of radiation and had undergone burrhole aspiration before treatment. Autopsy was refused on one patient who also appeared to have died from radionecrosis of the brain. Immunohistological examination in eight cases confirms that cerebral non-Hodgkin's lymphoma is a B-cell tumour. As other groups have found, its incidence appears to be rising. Survival rate is poor, and at least some deaths are related to both radiation necrosis and the bulk of residual tumour after diagnostic surgery.
Adult↗
Second malignancy in lymphoma.
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Age Factors↗
Angio-immunoblastic lymphadenopathy: a clinical, immunological and molecular study.
Twenty four patients with angio-immunoblastic lymphadenopathy (AILD) presenting between 1974 and 1985 have been reviewed. Clinical features at presentation included rash, fever, lymphadenopathy and hepatosplenomegaly in 75% of patients. Polyclonal hypergammaglobulinaemia was seen in 19/20 patients; 5 had normal immunoglobulin levels. Combination chemotherapy with MVPP was the optimal treatment with 6/7 patients achieving complete remission. Duration of remission ranged from 9 months to 4 years and was significantly longer in patients achieving complete as opposed to partial remission. In 6 patients phenotype studies were performed on single cell suspensions and immunoperoxidase studies on frozen sections of 7 lymph nodes. There was a reversal of the normal T suppressor/helper cell ratio with a predominance of T suppressor cells. Loss of normal B follicles was observed histologically in all except one lymph node. Germline configuration of the beta B-chain of the T cell receptor was observed in lymph nodes of 4 patients with AILD, and a rearranged T cell receptor was observed in 1 patient in whom a second lymph node biopsy had shown alteration of the histological picture to that of T-zone lymphoma. Frozen sera of 15 patients were screened for antibodies to HTLV I and III and were found to be negative.
Adult↗
The management of stage II supradiaphragmatic Hodgkin's disease at St. Bartholomew's Hospital. A retrospective review of 114 previously untreated patients over 14 years.
Between January, 1968 and July, 1981, 114 consecutive patients with newly diagnosed supradiaphragmatic stage II Hodgkin's disease were treated at St. Bartholomew's Hospital on the basis of pathologic staging (PS) in 56 (47 IIA, 9 IIB) and clinical staging (CS) in 58 (23 IIA, 35 IIB). Complete remission (CR) was achieved in 104 (91%) patients, of whom 27 have relapsed. Ninety-three patients remain alive, the cumulative predicted survival at 10 years being 81%, with a minimum follow-up of 2 years and a maximum of 15 years. Mantle radiotherapy (RT) was prescribed for 76 patients, of whom 67 (88%) entered CR. The duration of CR correlated inversely with the presence of intrathoracic lymphadenopathy. No patient with PS IIA and a normal chest radiograph has yet relapsed, whereas in contrast, a rising probability of relapse is related to increasing volume of intrathoracic lymphadenopathy. Combination chemotherapy (CT) with mustine, vinblastine, procarbazine, and prednisone (MVPP) was prescribed to 38 patients, 27 with "B" symptoms and 11 stage IIA patients with "unfavorable" features. CR was attained in 32 (84%) patients, of whom 24 subsequently proceeded to mantle irradiation. Only one of these has relapsed, compared to two of eight patients who did not receive adjuvant RT (P = NS). The duration of remission of patients receiving combined modality therapy (CT + RT) or CT alone was significantly longer (P less than 0.05) than that of patients receiving RT alone, in spite of the fact that the CT + RT group comprised predominantly patients with unfavorable features.
Adolescent↗
Characteristics of Sternberg-Reed, and related cells in Hodgkin's disease: an immunohistological study.
A panel of monoclonal antileucocyte antibodies was used in a study of Hodgkin's disease (HD) to explore the phenotypic characteristics of Sternberg-Reed and related cells (collectively termed HD cells). Cryostat preparations of 31 lymph nodes and 2 spleens were obtained from 30 patients with active HD. The histological diagnoses were: lymphocyte predominance (LP), 4 patients; nodular sclerosis (NS), 22; mixed cellularity (MC), 2; lymphocyte depletion (LD), 2. The monoclonal antibodies used were: OKT3, T11, Leu-1 (pan T cell specific); Leu-3A (T "helper" specific); Leu-2A, OKT8 (T "suppressor" specific); immunoglobulin (Ig) antibodies: anti kappa and lambda light chains, anti mu and delta heavy chains; B1 (anti B lymphocyte); CA2-11 (anti HLA-DR); OKM1, Mo-2 (anti myeloid/monocyte); OKT9 (anti transferrin receptor); Leu-7 (anti "NK" cell) and J5 (anti common ALL antigen). Reactions with peanut lectin (PNL) were also studied. The reactions were developed using a modified "ABC" immunoperoxidase technique. Specific attention was paid to the cell surface phenotype and anatomical localisation of HD cells in relation to surrounding T and B lymphocytes. HD cells formed distinct "rosettes" with T cells of "helper" phenotype although in 3 cases (1: LP, 2: NS) Leu-7 positive cells formed a prominent component of these interactions. In partially involved lymph node and spleen, HD cells were prominently distributed in a perifollicular distribution. In addition follicular mantle zones were frequently infiltrated by HD cells, the degree of ensuing destruction being related to the extent of lymph node effacement by HD. In 2 cases (1: NS, 1: LD) HD cells expressed clear, positive reactions with B1 although in neither of these cases nor in any other instance, was surface Ig expressed on the HD cell surface. The great majority of HD cells reacted positively with both OKT9 and, as previously reported, with anti HLA-DR antibody. In addition, HD cells demonstrated intense surface and cytoplasmic staining with PNL. HD cells were negative with all other antibodies. On the basis of these findings, no lineage specificity can confidently be attributed to the HD cell. However, the pattern of immunohistological reactions suggest that it is related to a cell of B follicular origins.
Adolescent↗
Adult Fanconi syndrome progressing to multiple myeloma.
A case of adult Fanconi syndrome is described in which there was urinary excretion of kappa light chains. After 13 years the patient developed overt myeloma. She also developed an adenocarcinoma of the colon and an adenocarcinoma of the parathyroid gland. These findings are discussed in relation to the known association between adult Fanconi syndrome, renal damage, and myeloma.
Adenocarcinoma, Papillary↗
The treatment of stage IIIA Hodgkin's disease.
Sixty consecutive previously untreated adults with surgically confirmed stage IIIA Hodgkin's disease (39 stage IIIA1, 21 stage IIIA2) began therapy at St. Bartholomew's Hospital between 1969 and 1981. Prior to 1973, treatment consisted of total nodal irradiation (TNI). From 1973 until 1978 patients were randomly allocated to receive either TNI or cyclic combination chemotherapy of mustine, vinblastine, prednisolone, and procarbazine (MVPP) as part of a Medical Research Council Trial. Since 1978 treatment has been allocated according to substage, those with stage IIIA1 receiving TNI and those with stage IIIA2 receiving MVPP. Seven patients received "non protocol" therapy (extended mantle radiotherapy in three patients, mantle and MVPP in four patients), and have been excluded from the study. Complete remission was achieved in 48 of 53 patients regardless of substage or therapy. Seven have relapsed, one after MVPP and six after TNI. The predicted freedom-from-relapse after MVPP was 96% compared with 60% after TNI, both at 10 years (p less than 0.01). The relapse pattern was the same for both substages in the group receiving TNI. Although overall survival of patients receiving TNI was identical to that of those receiving MVPP, TNI must be considered inappropriate therapy for stage IIIA Hodgkin's disease if permanent freedom-from-recurrence is the goal.
Adolescent↗
Distribution of T-lymphocyte subsets in Hodgkin's disease characterized by monoclonal antibodies.
Mononuclear-cell suspensions of lymph nodes, spleen and blood from 24 patients with active Hodgkin's disease (HD) were studied for possible imbalance of T and B lymphocytes, and T-lymphocyte subsets, using monospecific anti-T antibodies and other reagents. A profile showing T-cell predominance was demonstrated in lymph nodes and blood, with total T-cells ranging from 50-70% of the cell count. As defined by monoclonal antibodies, 70-85 of the latter comprised the "inducer" subclass, the remainder being "suppressor" cells. There were no essential differences between histologically involved and uninvolved lymph nodes from HD patients, though total T-cell proportions were lower in "normal lymph node" controls. The profiles of spleens electively removed, as part of pre-treatment staging procedures, showed reduced total T-cell numbers, whether these were involved with HD or not. These differences are accounted for principally by fewer T "inducer" cells (24%, in spleen, v. 54% in involved lymph nodes and 47% in "normal" control nodes). Possible explanations for these findings are discussed. Our results demonstrate similar profiles in histologically diseased and normal tissue, rather than any clear imbalance of T-cell proportions which might explain the profound disturbances of T-cell function frequently demonstrated in vivo and in vitro.
Adult↗
The management of localized, infradiaphragmatic Hodgkin's disease: experience of a rare clinical presentation at St Bartholomew's Hospital.
Between 1969 and 1982, 23 previously untreated patients with Hodgkin's disease (HD) confined to infradiaphragmatic sites were treated at St Bartholomew's Hospital. The distinguishing clinical characteristics of the patient population were a male: female ratio of 20:3. The mean age was 39 years, which was significantly older (P less than 0.05) than the mean age of patients with supradiaphragmatic HD (32 years) referred during the same period. Sixteen patients underwent formal pathological staging while one additional patient underwent a diagnostic laparotomy without splenectomy. The final pre-treatment stages were PS IA: 5; PS IIA: 11; CS IIA: 1; PS IIB: 1; CS IIB 5. Splenic involvement correlated closely with the number of nodal sites involved, being detected in 1/7 patients with one site only compared with 8/9 with more (P less than 0.001). Complete remission (CR) was achieved in 21 (91 per cent) patients: 12/12 following 'inverted Y' radiotherapy (RT) and 9/11 following combination chemotherapy. Twenty patients remain alive and 18 continue without recurrence of HD between 15 months and 12 years. All patients who failed to enter CR or who relapsed had presented with three or more sites of involvement or with constitutional ('B') symptoms. These results confirm the generally good prognosis of this uncommon presentation of HD and also suggest that prognosis is determined by the bulk of disease rather than its precise anatomical localization, provided that appropriate therapy is administered.
Abdominal Neoplasms↗
Second primary malignant neoplasms in patients treated for Hodgkin's disease at St Bartholomew's Hospital.
The incidence of second malignant neoplasms (SMN's) was investigated in a group of 529 patients with Hodgkin's Disease (HD) treated at St Bartholomew's Hospital (SBH). SMN's were seen in 27 of these patients giving an incidence rate three and a half times that expected in an age and sex matched normal population (p = much less than 0.001). The incidence rate was higher in those receiving multiple chemotherapy and radiotherapy for relapsed HD compared with those receiving primary radiotherapy, chemotherapy or chemotherapy with adjuvant radiotherapy (p = 0.02). However, the increased incidence rate in those patients treated with chemotherapy on relapse, may reflect in part a delayed effect of their primary therapy, since the incidence rate in the primary treatment group only becomes significantly raised after six years. When allowance was made for this delay the difference between the two groups was no longer significant. The incidence rates for Non-Hodgkin's Lymphoma (NHL) and myelogenous leukaemia were 32 and 57 times those expected, compared with only two and a half times the expected rate for non-haematological SMN's (p = much less than 0.001). The four acute myeloid leukaemias (AML) all occurred within five years of treatment compared to wide-ranging intervals between treatment and occurrence of SMN in the other groups. The increased incidence of NHL may be an alternative expression of lymphoid abnormality rather than a treatment-related occurrence. Multiple SMN's were diagnosed in three patients. This represented a highly significant (p = much less than 0.001) increase over the expected incidence of multiple neoplasia in the general population. Several factors may contribute to the development of SMN's in HD, including an inherent disposition of HD itself. The time-dependent incidence pattern of SMN's with a delay followed by an increased incidence rate, suggests that treatment plays a key role. It is not yet clear whether more intensive, or multiple treatments add to the risk accrued for the initial treatment.
Adult↗
Role of biological markers and probes in lung carcinomas.
Bronchial carcinomas are frequently associated with ectopic secretion of hormones which may be responsible for paraneoplastic syndromes. In non small cells carcinomas, serum calcitonin levels may be raised. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (responsible for gynaecomastia) in large cells carcinomas. In small carcinomas, many hormones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embryonic antigen add nothing to the information available with standard staging investigations. More recent studies have identified three protein products: the BB-isoenzyme of creatine kinase, bombesin and neurone-specific enolase. The latter seems a promising marker to follow up the course of the disease.
APUD Cells↗