Biomedical subjects
Publications and source records attributed to R K Knight.
Fistulation between the trachea and an infected mucocele arising from an excluded retained esophageal segment is an interesting and unusual complication of esophageal bypass surgery. We present such a case in which there was also malignant transformation in the cyst wall, manifested by invasive adenocarcinoma and widespread high-grade glandular dysplasia.
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Two cases of migration of totally implanted catheter systems are described. The complication is potentially life threatening.
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The outcome for 758 consecutive patients who had received one or more chemotherapy regimens for recurrent or metastatic breast cancer is presented. The response rate following first line treatment was 34%. Median duration of response was 7.8 months, median time to progression was 3.7 months and median survival was 7.9 months. The only factor predicting for response, of factors recorded at presentation and at initiation of chemotherapy, was the use of anthracycline based regimens, though this may reflect the patient selection policy. Initial disease free interval, presence of liver metastases and use of anthracyclines were significantly related to time to progression. Several factors related to survival following first chemotherapy, but anthracycline usage showed only a very weak correlation. One third of patients (249/758) received two or more chemotherapy regimens. The response rate (16%) and median time to progression (2.3 months) were significantly worse than for first line treatment. The outcome after third line chemotherapy was very similar to that observed following second line treatment. Achievement of an objective response with first line chemotherapy predicted for second response, but with insufficient power to be of use in selecting patients for subsequent chemotherapy. Time to progression following first line chemotherapy did not influence that after second line treatment.
Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.
We investigated the effect of pretransplant conditioning as a way to reduce the need for the aggressive immunosuppressive therapy reportedly required in small bowel (SB) allograft recipients. LEW rats were conditioned with (1) a donor-specific blood transfusion (DST) on day -8 and a concurrent 5-day course of CsA (10 mg/kg/day); (2) a nonspecific blood transfusion and CsA; (3) CsA alone. A 10-cm segment of the host native bowel was then replaced with an equivalent segment of SB obtained from ACI rats. Postoperative treatment consisted of CsA at 2.5 mg/kg/day for 30 days. Rats conditioned with a nonspecific transfusion and CsA or with CsA alone survived for 14.1 +/- 5.8 and 18.3 +/- 5.7 days, respectively. In contrast, rats conditioned with DST and CsA survived for 60.3 +/- 36.2 days (P less than 0.001 vs. both controls). Biopsies taken from long-term survivors showed a normal bowel architecture. The function of the allografts was studied in a group of animals totally deprived of their native bowel and transplanted with a 30-cm segment of ACI SB. CsA-DST-treated recipients survived an average of 90 +/- 43 days and grew at a rate comparable to isografted animals. Treated allograft recipients had maltose absorption indistinguishable from isografted controls at all times tested. In contrast, maltose absorption was severely impaired in recipients rejecting their grafts. This study demonstrates that long-term survival of SB allograft recipients can be achieved with good functional results with low doses of CsA in recipients conditioned with DST and CsA.
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Thirty-five patients with metastatic breast cancer and pericardial effusions are described. They were treated with specific endocrine or chemotherapy. Twenty-two (63%) had presented in cardiac tamponade and were rapidly relieved by pericardiocentesis. Eighteen (82%) of these required no further local treatment, 2 obtained relief from a second aspiration and 2 needed additional treatment (intrapericardial bleomycin instillation and surgical pleuropericardial window). The median survival was 13.2 months. No patient relapsed again in the pericardium, suggesting that their prognosis was that of the underlying disease. Cardiac tamponade should be considered in any breathless patient with malignancy. In breast cancer, periocardiocentesis is lifesaving and systemic treatment can usefully prolong life.
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Bronchoalveolar lavage (BAL) was performed in 47 patients (24 smokers, 18 ex-smokers and 5 who never smoked). Cytocentrifuged preparations were stained with May-Grunwald-Giemsa (MGG) and differential counts of pulmonary alveolar macrophages (PAM) with smokers' inclusions were performed. The data supported an exponential reduction in this percentage and indicated that about 3 years elapsed before this percentage approximated to the values in patients who had never smoked. Electron microscopy was performed on eight BALs and the results supported those obtained by light microscopy.
Forty-nine women with progressive metastatic breast cancer, extensively pretreated, received mitomycin C 12 mg/m2 and vinblastine 6 mg/m2 intravenously every 3 weeks. Eleven patients responded, giving a response frequency of 22%. Considering only the 40 patients evaluable after two or more courses of treatment, the response frequency is 27.5%. Responses occurred predominantly at soft tissue sites. Subjective toxicity was mild.
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Human alveolar macrophages, obtained during diagnostic bronchoscopy, were maintained in monolayer culture. Challenge of these cells (greater than 95% purity) with 1.2 mg/ml zymosan A particles (opsonized with human serum) was followed by a rapid release of leukotriene B4 into the medium, 7.28 +/- 5.99 ng/mg cell protein at 2 h (mean +/- S.D.4, n = 4). Leukotriene B4 was identified and measured by a novel technique employing capillary column gas chromatography coupled to negative ion chemical ionization mass spectrometry. The release of thromboxane B2, prostaglandins D2, E2, F2 alpha and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase was also measured. Thromboxane B2 was the most abundant metabolite of arachidonic acid released into the culture medium (65.2 +/- 14.8 ng/mg cell protein 2 h after the addition of zymosan A, n = 4), and the synthesis of thromboxane B2 was inhibited by greater than 90% in 1 microM Na flurbiprofen. Inhibition of cyclooxygenase activity was accompanied by a 2-fold increase in leukotriene B4 synthesis.
Adriamycin and mitomycin C in combination have been tested in the treatment of advanced breast cancer. In an initial pilot study 11 heavily pretreated patients received mitomycin C alone and 2 (18%) achieved partial responses. Subsequently, 27 patients who had not received prior chemotherapy for advanced breast cancer were treated with adriamycin 40 mg/m2 + mitomycin C 10 mg/m2 i.v. every 3 weeks. Six (22%) achieved complete and 10 (37%) achieved partial responses, giving an objective regression frequency of 59%. The median duration of response was 37 weeks (range 8-55+ weeks).