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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 145 records · Page 8Linked to original sources
PubMed1986

Is ectopic production of human chorionic gonadotrophin (hCG) or alpha fetoprotein (AFP) by tumours a marker of chemosensitivity?

We have treated eight patients with various tumours producing hCG or AFP with the high risk gestational choriocarcinoma regimen EMA/CO. Marker response was seen in two of three tumours producing AFP and in all of five tumours producing hCG. Three further patients were treated with EpPt/OMB, a regimen used in relapsed germ cell tumors. All responded biochemically. All complete biochemical responses were accompanied by anatomical response. These responses may reflect particular sensitivity in the marker producing tumours and marker measurements would identify this subgroup. These findings do not preclude the possibility that these cytotoxic regimens may have activity against a wide range of solid tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Current optimum management of anaplastic germ cell tumours of the testis and other sites.

Between 1977 and 1985, 149 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovine), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979, we have been able to compensate for adverse prognostic factors. Since then each patient has received at least three courses of POMB and 118 patients have completed therapy. The overall survival rate since 1979 is 89% and for the 100 patients who had not received prior radiotherapy it is 92%. We established that an initial serum concentration of human chorionic gonadotrophin (HCG greater than 50,000 iu/l) and/or alphafetoprotein (AFP greater than 500 ku/l) indicated a poor prognosis. Between 1977 and 1979 the survival rate in 12 patients in this category was only 45%. After increasing the number of courses of POMB, the survival rate rose to 89% in 31 patients. However, patients who had received prior radiotherapy and who presented with high tumour markers (HCG greater than 50,000 iu/l and/or AFP greater than 500 ku/l) continue to have a poor survival rate (20% in five patients). With this chemotherapy, 14 of 16 patients (88%) presenting with liver metastases and 6 of 7 patients (86%) presenting with brain metastases are in complete remission. Neither the stage at presentation nor the volume of metastatic disease was a major adverse prognostic variable. We believe that POMB/ACE chemotherapy, followed by surgery in selected cases, is currently the best treatment for patients with AGCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984).

Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1.1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.

Adult↗
PubMed1985

Gestational trophoblastic tumors.

Although virtually 100% of women who develop gestational trophoblastic tumors enter a long-term complete remission, there are many aspects of trophoblastic disease that arouse interest. Epidemiological studies have shown a large geographical variation in the percentage of conceptions that result in a hydatidiform mole and have stimulated studies on the immunological differences of the low and high risk populations. Chromosomal analysis is now complementing the pathological differentiation between complete and partial moles. There is still debate as to which factors are positively associated with the progression of a hydatidiform mole through invasive mole to choriocarcinoma. There are also considerable differences in the proportion of molar patients receiving chemotherapy in different centers. In addition to these topics, this article will review several recently introduced treatment regimens which show improved results with reduced toxicity.

ABO Blood-Group System↗
PubMed1984

Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours.

To examine the possibility that cytotoxic drugs may cause sterility or congenital malformations in the offspring of women of childbearing age who are cured of cancer a study was conducted of the obstetric histories of 445 long term survivors treated in this unit with chemotherapy for gestational trophoblastic tumours between 1958 and 1978. After completing treatment 97% of those who wished for a pregnancy (49% of all women studied) conceived and 86% had at least one live birth. All these women had received methotrexate. Of the 47 women who wished to conceive and whose combination therapy included cyclophosphamide, 37 (79%) had a live birth. Women who received three or more drugs were less likely to have a live birth than those who received methotrexate alone or with only one other drug (p less than 0.001). There was no statistically significant excess of congenital malformations. These results are strong evidence that the cytotoxic drug regimens used in this unit for treating gestational trophoblastic tumours are compatible with the preservation of fertility in most women and not associated with any increase in congenital abnormalities.

Abnormalities, Drug-Induced↗
PubMed1984

Response of differentiated but not anaplastic teratoma to interferon.

A Phase 2 trial was conducted using intramuscular lymphoblastoid interferon (IFN, Wellcome Research Laboratories), 4 MU per day, in 10 patients with chemotherapy-resistant teratomas. There was stabilisation of disease in 2 patients both of whom were in retrospect considered to have had differentiated teratoma at the time of IFN administration. There was progression of presumed active anaplastic germ cell tumour in 8 patients. One of these patients, a 15-year-old boy with biopsy proven differentiated teratoma has received 2 courses of lymphoblastoid IFN and 1 course of recombinant leukocyte A IFN (Roche Products Ltd.) lasting 5 1/2, 8 and 8+ months respectively. He has had a mixed response in his differentiated tumour which on each occasion has been maintained for the duration that he received IFN. Rising HCG levels during his second course of interferon required additional cytotoxic chemotherapy. Lymphoblastoid IFN does not appear to be active against anaplastic germ cell tumours but both lymphoblastoid and recombinant leukocyte A IFN may be useful in the treatment of unresectable differentiated teratoma.

Adolescent↗
PubMed1983

Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital.

Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty-nine (8.8%) patients had central nervous system (CNS) metastases. Thirty-three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life-table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.

Adult↗
PubMed1983

Further advances in the management of malignant teratomas of the testis and other sites.

Between 1979 and 1982, 69 men with metastatic malignant teratoma completed sequential combination chemotherapy (POMB/ACE). Although two-thirds of these patients initially had advanced and bulky disease, life-table analysis projects a survival of 83%. Multivariate analysis indicates that the strongest predictor of survivals is not the clinical and radiological extent of disease but the initial serum concentration of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP). In patients presenting with HCG levels below 50 000 IU/l and AFP levels below 500 kU/l the survival in 47 patients was 96%. This contrasts with the survival projected at 56% in 22 patients presenting with tumour markers at higher concentrations.

Antineoplastic Agents↗
PubMed1983

No increase in second tumors after cytotoxic chemotherapy for gestational trophoblastic tumors.

We investigated the incidence of second tumors after cytotoxic chemotherapy in 457 long-term survivors treated for choriocarcinoma or an invasive mole between 1958 and 1978. Treatment was given according to regular intermittent schedules and over a mean period of four months, with no maintenance. Methotrexate was given to all but two patients, and 261 (57 per cent) also received other cytotoxic drugs, most commonly dactinomycin, vincristine, cyclophosphamide, mercaptopurine, and 6-azauridine. After a mean period of 7.8 years since the beginning of treatment and a total of 3522 patient-years of risk, second neoplasms had developed in only two women (acute leukemia in one and carcinoma of the breast in the other). This figure is less than the number of cases of cancer that would have been expected (3.5) in this group and suggests that the use of methotrexate as chemotherapy for choriocarcinoma is not carcinogenic in the medium term.

Adult↗
PubMed1983

Effective treatment for malignant mediastinal teratoma.

Primary malignant mediastinal teratoma is a rare tumour previously regarded as inevitably fatal. In a series of eight male patients with a mean age of 24 years five remain alive and well. All patients showed raised serum concentrations of human chorionic gonadotrophin or alpha fetoprotein. The patients were treated with intermittent combination chemotherapy that included cisplatin. Six patients responded to chemotherapy with a fall in human chorionic gonadotrophin or alpha fetoprotein to near normal levels and they then had radical excision of the remaining tumour. Living malignant tumour was found in four of the specimens and these patients received postoperative chemotherapy. One patient died after eight months and the remaining five patients are alive and well 13-136 months after the start of treatment. The two patients who did not undergo surgery died at one month and 15 months. Intermittent combination chemotherapy and carefully timed radical excision of these tumours would appear to have produced better results than have been reported in other series.

Adolescent↗
PubMed1982

The role of abdominal surgery in the treatment of advanced testicular germ cell tumours.

Twenty patients with advanced testicular teratoma and 1 with advanced seminoma have undergone abdominal surgery for the removal of residual disease following treatment by sequential chemotherapy (1). Fourteen out of the 21 patients (66 per cent) have achieved complete remission with a follow-up period of 6--41 months. In 12 patients (57 per cent) the tumour had undergone histological maturation or necrosis following chemotherapy, those patients in whom the tumour remained histologically active having a worse prognosis. Raised preoperative serum levels of the tumour markers human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) indicating active disease, forecast a particularly poor prognosis, 5 out of 9 such patients (55 per cent) having died. Computerized tomography gave false negative results in 3 patients (14 per cent). Postoperative complications were few, and 2 patients (9 per cent) suffered with failure of ejaculation. At present our policy is surgical removal of any residual mass after chemotherapy to determine the histology, and, wherever possible, to achieve complete clinical and biochemical remission. Six patients with an apparently poor prognosis have benefited directly from surgery and remain in long term remission. The selection of patients who benefit most from surgery can only be determined by more experience and longer follow up.

Adolescent↗
PubMed1982

Potential for cure in metastatic ovarian teratomas and dysgerminomas.

Between 1977 and 1981 21 patients with metastatic ovarian germ cell tumours received sequential combination chemotherapy; 18 had malignant teratomas and three dysgerminomas. Thirteen patients with malignant teratoma have had no treatment for up to 45 months (mean 27.5 months) and one patient is still having treatment. Life table estimate of survival on 1 July 1981 projects a survival of 71% in those with malignant ovarian teratomas. Four patients with malignant teratoma have died. Two of these had received extensive treatment before referral and a third achieved complete remission but relapsed and did not subsequently respond fully to further treatment. A fourth patient had an undifferentiated tumour compatible with an embryonal carcinoma which proved refractory to all treatment. The three patients with advanced dysgerminomas are all in remission and have had no treatment for 5, 14 and 33 months respectively. The majority of metastatic germ cell tumours of the ovary now appear to be curable provided that effective treatment is begun early.

Adolescent↗
PubMed1981

The ultrastructural localization of human neutrophil alkaline phosphatase in normal individuals during pregnancy and in patients with chronic granulocytic leukaemia.

The intracellular localization of alkaline phosphatase was determined in human neutrophils by electron microscope cytochemistry. In normal individuals, the largest and most intense deposits of reaction product was seen in a unique cytoplasmic granule population termed 'phosphasomes'. Lighter deposits were seen on nuclear membranes, some intracytoplasmic membranes lining vacuoles and granules and occasionally in focal patches on the internal surface of the plasma membrane. In cells isolated from women in the third trimester of pregnancy, activity was found in the same intracellular sites but there were, on average, more alkaline phosphatase-containing granules per cell than in the cells from non-pregnant individuals. Neutrophils from pregnant women were also characterized by the presence of large deposits of reaction product on the external surface of the plasma membrane (extramembranous). This activity had properties characteristic of the placental isoenzyme of alkaline phosphatase, found in serum during pregnancy. Neutrophils from patients with chronic granulocytic leukaemia, showing normal mature morphology, contained significant amounts of granule reaction product but there were fewer phosphasomes per cell than in normal individuals. In morphologically immature cells, reaction product was present in nuclear membranes, endoplasmic reticulum and large granules. These results were in agreement with previous biochemical data confirming a quantitative lack of alkaline phosphatase in chronic granulocytic leukaemia.

Alkaline Phosphatase↗
PubMed1981

Electron microscopic cytochemical localization of nucleoside phosphatases in normal and chronic granulocytic leukaemic human neutrophils.

Using electron microscope cytochemistry and cells separated on Ficoll-Hypaque, Mg2+-dependent ATPase, ADPase and 5'-nucleotidase were predominantly localized as ectoenzymes on normal human granulocytes. Large deposits of ATPase final reaction product and more finely granular deposits of 5'-nucleotidase final reaction product were firmly attached to the outer surface of cell plasma membranes. The final reaction product from ecto-ADPase was, however, only loosely associated with the plasma membrane. In addition, finer deposits of ADPase final reaction product were seen in specific granules and in background cytoplasm. No nucleotidase phosphatase activity was localized to the alkaline phosphatase-containing granules (phosphasomes) recently described by Rustin et al. In granulocytes from patients with chronic granulocytic leukaemia, ecto-ATPase had a patchy distribution on the plasma membranes. There was considerable heterogeneity between cells with regard to ADPase and 5'-nucleotidase localization. In some cells, ADPase was seen only at both site, while in some cells no activity was detected. 5'-Nucleotidase localization was normal in some cells but lacking from many. No correlation was found between enzyme heterogeneity and the degree of morphological cell maturity.

5'-Nucleotidase↗