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Biomedical subjects

M F Spittle

Publications and source records attributed to M F Spittle.

At least 37 records · Page 2Linked to original sources

Radiotherapy is a useful treatment for lymphangioma circumscriptum: a report of two patients.

Lymphangioma circumscriptum is a rare non-malignant skin tumour, conventionally treated by surgical resection, but with variable results. We report two cases, which, although unsuitable for excision, were treated successfully by radiotherapy and consider the place of this modality in managing this disorder. We conclude that radiotherapy is an effective treatment for unresectable lesions, or for patients who are unwilling to consider surgery.

Adult↗

Management of cutaneous lymphoma.

The foregoing underlines the advances which have been made in our understanding of cutaneous lymphoma and the areas where further research is needed. With a few noteable exceptions the aim of therapy in CTCL is palliative rather than curative and treatment success is measured in terms of disease-free interval. There is still no evidence that any chemotherapeutic regimen prolongs survival. A possible exception is the effect of photopheresis in Sézary syndrome but our own experience differs from that in the USA and underlines the need to identify patients with clonal disease when defining subjects for study. The combination of genotypic analysis and new treatment methods offers exciting new prospects in the management of patients with cutaneous lymphoma.

Humans↗

Phase II study of gemcitabine in patients with advanced pancreatic cancer.

The efficacy and safety of gemcitabine at a starting dose of 800 mg m2 administered once a week for 3 weeks with 1 week's rest was investigated in chemonaive patients with advanced and/or metastatic pancreatic cancer. Of 34 patients, 32 were evaluable for efficacy, 20 patients had metastatic stage IV disease, 25 had a performance status of 1 and 26 (76%) patients has significant pain on presentation. All responses were independently validated by an external oncology review board: two patients achieved a partial response that lasted 5.8 and 5.2 months (6.3%) and six patients were stable for at least 4 weeks. The median duration of survival for evaluable patients was 6.3 months (range 1.6-19.2 months). The tumour markers, CEA, CA 19-9 and CA 195 were serially measured in 16 patients. There was a good correlation with tumour response when all three markers were significantly decreased. In 4 of 16 patients, tumour marker levels decreased by > or = 60%, including the two responders, one patient who survived for 12 months and one patient who showed objective tumour shrinkage but was deemed ineligible for response evaluation because the disease was considered not to be bidimensionally measurable. Symptomatic benefits included improvement in performance status (17.2%), analgesic requirement (7.4%), pain score (28.6%) and nausea (27.3%). The mean number of cycles administered was 2.5 and the mean dosage received was 890 mg m2 per injection. Seventy-four per cent of dose administrations were given on schedule. Toxicity, particularly haematological toxicity, reported as the maximum WHO grade experienced by patients was mild. Infective episodes were rare and limited to WHO grade 2 (6.7%). Nausea and vomiting was generally modest (WHO grade 3, 26.7%). Other side-effects included mild transient flu-like symptoms (seven patients) and peripheral oedema (three patients), which was not associated with abnormal cardiac hepatic or renal function. Gemcitabine has modest activity in pancreatic cancer, a limited positive improvement on a range of patient benefit parameters and has a mild toxicity profile. For these reasons and because of its novel mode of action, gemcitabine warrants further investigation in combination studies in pancreatic cancer.

Adult↗

Management of malignancy in HIV infection.

The prevalence of HIV-related malignant disease is increasing, probably due to more effective management of opportunistic infection. The most frequent tumours are Kaposi's sarcoma, systemic non-Hodgkin's lymphoma and primary central nervous system lymphoma. Management of these conditions must take into account host indicators of immunosuppression and prognostic outcome in order to minimise treatment associated complications.

HIV Infections↗

A retrospective comparison of endoscopic stenting alone with stenting and radiotherapy in non-resectable cholangiocarcinoma.

BACKGROUND AND AIMS: Radiotherapy has been reported to be of benefit in prolonging the survival of patients with cholangiocarcinoma. This study examined whether radiotherapy in addition to endoscopic stenting improved survival. SUBJECTS: 56 patients with obstructive jaundice due to histologically confirmed non-resectable cholangiocarcinoma. METHODS: A retrospective analysis of these patients who were treated either with endoscopic biliary stenting followed by external beam radiotherapy and internal iridium-192 brachytherapy (n = 28) or with stenting alone (control group; n = 28). RESULTS: The two groups were well matched in age, sex, and stricture type. Eighteen patients had a type I stricture (control group: 11; radiotherapy group: 7) at the time of diagnosis and 38 had a type II or III stricture (control group: 17; radiotherapy group: 21). The median (range) overall survival from diagnosis was seven (1-29) and 10 (4-75) months in the control and radiotherapy groups respectively: This difference did not reach statistical significance (p = 0.06), but survival plots indicated a survival advantage in the radiotherapy group in the first nine months after diagnosis. Approximately one third survived longer than one year in both groups. More patients in the radiotherapy group required a stent change (1.9 v 0.9: p = 0.05), and also had a longer overall inpatient stay (42 days v 19: p < 0.001). When examined on the basis of stricture type, there was a survival advantage in the first 10 months after diagnosis in those with a type II/III stricture (seven and 11 months in the radiotherapy and control groups respectively: 0.01 < p < 0.05). There was no difference in survival between the groups in those with a type I stricture. Numbers surviving longer than one year, stent survival, and number of stent changes were all similar between the two groups when examined on the basis of stricture type, but length of hospital stay remained considerably longer in all patients receiving radiotherapy. CONCLUSION: The survival advantage of radiotherapy in those with a type II/III stricture is seen only in the first 10 months after diagnosis. The costs of radiotherapy and significantly increased time spent in hospital, however, raise doubts over its routine use in the management of non-resectable cholangiocarcinoma.

Aged↗

AIDS-related malignancies.

The management of AIDS-related malignancies demands that the cancer must be treated in the context of patients already suffering from a fatal disease. Management must be problem-orientated. The standard cancer treatment of such a patient may not be appropriate in the AIDS setting. The AIDS related malignancies are Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) including primary cerebral lymphoma. Carcinoma of the cervix was recently added to this list, but has not been seen in this context in the UK.

Acquired Immunodeficiency Syndrome↗

Targeting disseminated melanoma with radiolabelled methylene blue: Comparative bio-distribution studies in man and animals.

Targeted radiotherapy for pigmented melanoma with 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with Astatine-211 (211At; alpha-particle emitter) proved to be very effective in animal model systems. Since the results justified an introduction of the treatment to the clinic, the aim of the bio-distribution studies using [123I]-MTB and [131I]-MTB in patients was to confirm selectiveness of radiolabelled MTB uptake in melanoma lesions. The investigations were carried out using planar and SPECT (single photon emission computed tomography) gamma-cameras. A stable uptake of radioiodinated MTB was found in pigmented melanomas in man, with tumour/surrounding tissue and tumour/blood ratios amounting to 9 at 19 h after a single i.v. injection. A time-dependent kinetics of radioiodinated MTB distribution was similar to that observed in human melanoma-bearing athymic mice. Blood radioactivity decreased by about 90% during the first 2.5 min after i.v. injection of the compound (T1/2biol = 0.58 min). Its retention time in various organs was either the same or very similar to that characteristic of the blood. A rapid uptake of radioiodinated MTB in the liver and kidneys confirmed the importance of these organs in excreting the compound: 25-30% of the radioactivity administered was expelled with urine over the first 24 h after the injection. There was no obvious retention of radioiodinated MTB in the brain over the observation period and in the eyes for at least the first 14 h.

Adult↗

Oncological problems in AIDS--a review of the clinical features and management.

Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic in the early 1980s, several malignant conditions have been recognised to be associated with this syndrome which affect up to 40% of AIDS patients at some stage of their illness. They include Kaposi's sarcoma, systemic non-Hodgkin's lymphoma, primary central nervous system lymphoma and invasive cervical cancer. Kaposi's sarcoma and primary central nervous system lymphoma were tumours rarely seen below the age of 50 prior to the epidemic and therefore were recognised early to be AIDS-related conditions. However, systemic non-Hodgkin's lymphoma and invasive cervical cancer were only recognised when sufficient epidemiological evidence became available to indicate an increased incidence of these conditions amongst the HIV-infected population. In the presence of immunosuppression, the biological behaviour of these conditions are significantly altered with a more advanced stage at presentation, a more aggressive disease course and poorer responses to treatment. There is evidence that in each of these malignant conditions, an additional viral infection may be responsible for their pathogenesis. Kaposi's sarcoma-associated herpes virus is implicated in the development of Kaposi's sarcoma, Epstein-Barr virus in systemic non-Hodgkin's lymphoma as well as primary central nervous system lymphoma and human papilloma virus in invasive cervical cancer. Developing effective treatment strategies with minimal toxicity for these patients remains the greatest challenge as they often have serious coexisting illnesses and tolerate chemotherapy poorly because of insufficient bone marrow function reserve.

AIDS-Related Opportunistic Infections↗

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom.

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.

Adult↗

Can long-term survival be improved in patients with small-cell lung cancer (SCLC) and good performance status? Medical Research Council Lung Cancer Working Party.

Results from a long-term follow-up suggest that in patients with limited small-cell lung cancer (SCLC) and normal performance status intensive alternating chemotherapy and radiotherapy improve long-term survival rates. In a non-randomised study, 22 patients with SCLC of limited extent and good performance status were prescribed six cycles of etoposide, doxorubicin, cisplatin and cyclophosphamide at 4 week intervals with doses of thoracic radiotherapy following the second, third and fourth cycles. Although only six patients received all their prescribed treatment, nine (41%) were alive at 1 year, seven (32%) at 2 years, six (27%) at 3 years, and four are still alive at, respectively, 42, 47, 50, and 61 months, all four being in the subgroup of eight patients with WHO performance status grade 0 at the start of treatment. In a comparison with similar patients receiving conventionally scheduled chemotherapy and radiotherapy in a concurrent trial, no difference in survival was seen in the patients with performance status grade 1 or 2, but a large difference in favour of the alternating schedule in those with grade 0 status was seen. We encourage other investigators to report the results achieved with intensive treatment in patients with WHO grade 0 performance status at the start of treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis fungoides.

The development of extensive cutaneous necrosis in a patient with tumour-stage mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate, and thrombosis of dermal blood vessels. Investigation revealed the presence of anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which contributed to a prothrombotic state. Antiphospholipid antibodies have been detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon. Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency with which antiphospholipid antibodies occur in mycosis fungoides is currently unknown.

Antiphospholipid Syndrome↗

Liposomal doxorubicin for treatment of AIDS-related Kaposi's sarcoma.

Sixteen patients with advanced AIDS-related Kaposi's sarcoma received liposomal doxorubicin (Doxil, Liposome Technology, Menlo Park, California) at 20 mg/m2 every 2 or 3 weeks in an open label study, and were evaluated for efficacy and toxicity. Eleven patients achieved a partial remission and five had stable disease. The median time to achieve a maximum response was two cycles (range 1-3) and the median duration of response was 14 weeks (range 6-30). Myelosuppression was the commonest adverse event; one patient was withdrawn because of neutropenia. Other adverse events were uncommon and mild. Liposomal doxorubicin is an effective and safe single agent treatment for advanced AIDs-related Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Five case reports of high grade non-Hodgkin's lymphoma in human immunodeficiency virus-1 negative homosexual men.

High grade non-Hodgkin's lymphoma accounts for only 5%-10% of all non-Hodgkin's lymphoma. Infection with the human immunodeficiency virus increases the risk of developing high grade, usually B-cell, lymphoma, which has been noted to occur more commonly in homosexual men. These lymphomas often have unusual clinical presentations. We report five cases of high grade non-Hodgkin's lymphoma in HIV negative homosexual men who presented to our hospital in a 13-month period. As a major centre for the treatment of the acquired immune deficiency syndrome, there may be a self-selected homosexual population attending for medical care, and thus a bias in the relative incidence of lymphoma seen in this group.

Adult↗

Hodgkin's disease: a case of late relapse.

A case of Stage 1 nodular lymphocytic predominant Hodgkin's Disease relapsing after 32 years is described. Recent immunophenotyping suggests that this is a low grade B-cell lymphoma.

Adult↗

A comparison of doxorubicin, epirubicin and mitozantrone as single agents in advanced breast carcinoma.

Between July 1985 and December 1987, 87 patients with advanced breast carcinoma were randomized to receive single agent doxorubicin (70 mg/m2), epirubicin (70 mg/m2) or mitozantrone (14 mg/m2) at 3-weekly intervals. The patients had received no previous chemotherapy for their advanced disease but 91% had received prior hormonal therapy. The response rates were 36% with doxorubicin, 32% with epirubicin and 26% with mitozantrone, but these differences did not reach statistical significance. The median survival of all patients was 8.3 months. There was no significant difference in response rates or survival according to menopausal status. The toxicities of the three agents are compared. Nausea, vomiting and alopecia were more severe in patients treated with doxorubicin or epirubicin than those treated with mitozantrone. Myelosuppression and infective episodes occurred more frequently with mitozantrone. Two cardiac complications were reported. This study shows that the toxicity and low efficacy of all three agents limit their use as single agents in advanced breast carcinoma. The role of single agent chemotherapy and the relative toxicities of these drugs are discussed.

Adult↗