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Biomedical subjects

J K MacFarlane

Publications and source records attributed to J K MacFarlane.

At least 37 records · Page 2Linked to original sources
PubMed1991

Detection of micrometastases from primary breast cancer.

The monoclonal antibody LICR-LON-M8 was used in a series of experiments to determine how an immunohistochemical technique could be used as a diagnostic test for micrometastatic disease in patients with operable, primary breast carcinoma. Optimal tissue and antigen preservation was obtained with fixatives containing either picric acid or a heavy metal such as mercury to allow staining with the monoclonal antibody diluted to 1:12,000 to 1:16,000 from unpurified mouse ascites. Tissue affected by primary and metastatic disease stains in a characteristic fashion, which is distinct from benign breast tissue. All the ductal tumours stained positively for malignant cells with the monoclonal antibody preparation. Within the bone marrow, occasional granulocytes and granulocyte precursors stained positively if the endogenous peroxidase activity was incompletely blocked. These cells were readily differentiated from tumour cells on cytologic examination. With these monoclonal antibody and immunohistochemical staining techniques it may now be possible to detect early micrometastatic disease in the bone marrow of patients with primary breast cancer.

Antibodies, Monoclonal↗
PubMed1991

Monoclonal antibody LICR-LON-M8 does not predict the outcome of operable breast cancer.

The prognostic value of the monoclonal antibody LICR-LON-M8, which has been shown to detect micrometastatic disease, was evaluated in a prospective, double-blind, clinical study of bone-marrow specimens from patients with operable breast cancer. Four bone-marrow specimens, obtained from each of 50 patients at the time of excision of the primary breast tumour, were examined immunohistochemically, with LICR-LON-M8 as the primary antibody. All of the primary tumour specimens demonstrated positive staining for malignant disease with LICR-LON-M8. The bone-marrow specimens of four patients demonstrated positive staining: three specimens were "suspicious" for malignant cells and one contained definite malignant cells on cytologic examination. This gave a 2% rate of detectable micrometastatic disease at the time the primary tumour was excised. Patient follow-up averaged 21.5 +/- 9.1 months. The test results did not correlate with outcome. A negative test result with LICR-LON-M8 did not imply a better prognosis. The authors conclude that examination of bone-marrow specimens stained with LICR-LON-M8 in patients with operable breast cancer is of no clinical value. Furthermore, the low rate of micrometastases detected is at variance with that reported by others. In view of the natural history of breast cancer, the authors believe that their results were not unexpected and they question the importance of other results.

Adult↗
PubMed1991

Detecting breast cancer after reduction mammoplasty.

Reductive breast surgery may give rise to parenchymal scarring that makes subsequent clinical and radiologic assessment of tumours difficult. The features that help distinguish benign from malignant lesions are discussed. Biopsy is still necessary. A screening protocol that includes preoperative mammography in patients at increased risk is proposed.

Breast↗
PubMed1990

Fine needle aspiration cytology in the evaluation of head and neck masses.

One hundred eighty-two fine needle aspirations (FNAs) of head and neck masses performed between the years 1981 and 1987 were studied retrospectively. Seventeen FNAs were unsatisfactory. Of the remaining 165, 148 (90%) were followed up with either surgery or clinical follow-up of at least 12 months' duration. Seventy-one of these aspirates were malignant. Fifty-six cases of metastatic carcinoma and 13 cases of lymphoma were diagnosed. The positive predictive value for metastatic carcinoma and lymphoma was 100%, and the sensitivities were 92% and 100%, respectively. For benign salivary gland lesions, the positive predictive value was 94%, whereas for malignant lesions it was 100%. One case of carcinoma ex-pleomorphic adenoma was missed by FNA. No complications were associated with FNA. We conclude that FNA is a safe and accurate technique, well suited to the in-office evaluation of neck masses of differing causes.

Biopsy, Needle↗
PubMed1990

Preoperative radiotherapy for adenocarcinoma of the rectum.

Curative surgery remains the principal treatment for rectal carcinoma. Unfortunately failure following surgery, particularly through local recurrence, is an all too common event. Among the potential adjuvant therapies, preoperative radiotherapy holds clear promise. A review of the clinical trials evaluating this treatment modality shows that it can decrease the rate of local recurrence and may even improve the overall 5-year survival. Preoperative radiotherapy is consistently well tolerated up to doses as high as 60 Gy; it does not complicate the surgical resection or increase the perioperative morbidity and mortality. Preoperative radiotherapy warrants further investigation to select those patients who are most likely to benefit from it.

Adenocarcinoma↗
PubMed1990

Follow-up of patients who have undergone ileogastrostomy.

Patients who have had ileogastrostomy for the treatment of morbid obesity require close, long-term follow-up. From a prospective study of a large number of variables in 12 consecutive patients, and from experience with more than 200 patients who have undergone this procedure since 1982, a protocol has evolved. The authors outline the associated morbid conditions, operative complications and biochemical alterations that are important in the management of these patients.

Gastric Bypass↗
PubMed1986

Ambulatory hepatic artery infusion chemotherapy for cancer of the liver.

We have used continuous hepatic arterial infusion chemotherapy to treat 105 patients with cancer of the liver originating from colorectal, other gastrointestinal, and nongastrointestinal sites. The response rate seen in colorectal metastases was two to three times that expected for systemic chemotherapy. The median survival of responders of 16 months was significantly better then for nonresponders (6 months). The median duration of response was 9 months. The results for patients with other tumor types were less encouraging. Although minor problems developed in about 30 percent of the patients, major complications requiring removal of the catheter were not common. Expertise derived from managing many patients and a team approach, with a defined protocol for catheter care and follow-up, contributed to the success of the ambulatory program. However, the role of hepatic arterial infusion chemotherapy remains under debate. At the root of the controversy is the lack of randomized, controlled trials supporting the superiority of hepatic arterial infusion over systemic chemotherapy in the treatment of colorectal liver metastases. This and other issues, including the current liberal use of implanted infusion pumps, should be studied.

Adult↗
PubMed1984

Requirement for autologous cancer extracts and lipoxygenation of arachidonic acid for human T-cell responses in leukocyte adherence inhibition and transmembrane potential change assays.

Assays of leukocyte adherence inhibition (LAI) and transmembrane potential (delta psi) change were used to examine the responses of T-cells from control subjects and breast cancer patients when incubated with extracts of breast cancer and other tissues. Of T-cells from 25 patients with breast cancer, 21 exhibited delta psi changes or inhibition of adherence to glass when they were incubated with extracts of autologous but not allogeneic breast cancer; extracts of autologous normal breast tissue did not induce delta psi changes or LAI in T-cells from patients with breast cancer. Supernatants were collected after incubating 1 X 10(7) T-cells from patients with breast cancer or from control subjects with extracts of the autologous cancer. When the supernatants were added to either peripheral blood leukocytes or mononuclear cells from normal donors, neither delta psi changes nor LAI were detected. To still determine whether the nonadherence was mediated by chemoattractant lymphokines, the effect of inhibiting T-cell arachidonic acid metabolism was examined. The lipoxygenase pathway antagonist, 5,8,11,14-eicosatetraynoic acid, or a leukotriene antagonist, FPL 55712, inhibited T-cell LAI, but a cyclooxygenase pathway antagonist, indomethacin, did not. Moreover, authentic leukotriene B4 induced delta psi changes and LAI in T-cells. The results indicated that T-cells from patients with breast cancer recognized and bound a tumor-specific antigen in the autologous neoplastic breast tissue that transduced a transmembrane signal to trigger a series of biochemical changes, releasing lipoxygenase products of arachidonate. The lipoxygenase products, which may be important in the inflammatory response to cancer, induced a loss of T-cell adherence to glass.

Arachidonic Acid↗
PubMed1982

Predictive value of tube leukocyte adherence inhibition (LAI) assay for breast, colorectal, stomach and pancreatic cancer.

The tube LAI assay measures accurately antitumor immunity in patients with early cancer but fails to detect up to 75% of patients with advanced cancer due to excess circulating organ-specific neoantigen (OSN). Substances such as prostaglandin E2 (PGE2) or aminophylline, which increase intracellular nucleotides in leukocytes of patients with advanced cancer reversed this nonreactivity and greatly increased the sensitivity of the assay without any loss of specificity. Antitumor immunity can now be detected in advanced cancer, and a combination of the two assays gives prognostic potential to the assay: a positive test with PGE2 and negative test without indicates the patient has a large tumor burden. The specificity of the assay for each cancer was high and in most instances was greater than or equal to 95%. The PGE2 stimulated assay retained the high specificity. The sensitivity of the regular tube assay was often low, 33-56% because of the many advanced cancer patients tested, whereas the PGE2 stimulated assay showed almost a two-fold increase in sensitivity, 67-93%. The diagnostic value of the assay was estimated by calculating the predictive value for different prevalences of cancer. It was found that at low prevalences of cancer as found in the general population, the assay had a low diagnostic value since few patients with a positive test would have the cancer tested for. With prevalences of cancer of 5% or greater as might be found in a tertiary care clinical setting, the assay would seem to have diagnostic value since one half or more patients with a positive test would have the cancer tested for. Most false positives, but not all, are found in patients who have lesions that are often considered to increase their risk for cancer: severe dysplasia of the breast, colon adenomas, chronic atrophic gastritis and chronic pancreatitis, suggesting that the assay predicts oncogenesis.

Aminophylline↗
PubMed1981

A comparison of tube leukocyte adherence inhibition assay and standard physical methods for diagnosing colorectal cancer.

In vitro antitumor immunity, measured by means of a tube leukocyte adherence inhibition (LAI) assay, was able to demonstrate early colorectal cancer in cases yet undiagnosed. Testing 106 patients attending a colonoscopy clinic, we found that nine of 15 (60%) patients with colorectal cancer were LAI-positive. The nine included: five of six with Dukes' A and B; one of two with Dukes' C; and three of seven with Dukes' D lesions. Of 58 patients without colon neoplasia, one had a positive test. By contrast, barium enema results were diagnostic for 13 of 15 (87%) cases and colonoscopy for 11 of 15 (73%). There were 32 colon polyps discovered by means of barium enema and colonoscopy. Of 13 adenomas removed, four had stimulated positive LAI responses. Of another 19 polyps not removed two incited positive LAI responses. Two patients with histories of recurrent adenomas were LAI-positive, though only one had a new polyp that could be detected by means of barium enema. For a procedure to be of diagnostic value for a given disease, sensitivity and specificity must be at least 1.0. If this sum is 2.0, the test is ideal. The sum of sensitivity and specificity for the tube LAI assay, barium enema, and colonoscopy were 1.58, 1.87, and 1.73, respectively, for colorectal cancer; 1.81, 2.0, and 2.0, respectively, for early colorectal cancer; and 1.42, 1.77, and 1.55 respectively, for advanced colorectal cancer. In this limited series of patients, the barium enema seems to be superior to the tube LAI assay for diagnosing colorectal cancer, but the difference in sensitivity and specificity is not statistically valid by the paired chi square test. The results of this study shows conclusively, that the tube LAI is of diagnostic value and suggest its use for evaluating suspected cases, especially early ones, of colorectal cancer.

Adenoma↗
PubMed1981

A coded study of antitumor immunity to human lung cancer assayed by tube leukocyte adherence inhibition.

The present study was undertaken to evaluate the specificity of antitumor immunity to human lung cancer, measured by an in vitro assay--tube leukocyte adherence inhibition (LAI). We standardized and monitored the putative tumor antigen activity of the extracts by testing leukocytes from controls and patients with lung cancer in the Montreal General Hospital. A specific antitumor response to a lung cancer antigen was detected with coded leukocytes from 56% (20 out of 36) of patients with epidermoid lung cancer. By contrast, 4% (2 out of 53) of patients with inflammatory lung disease and none of 46 other patients with cancer metastatic to the lung or with other diagnoses had an LAI-positive result. The LAI response was inversely related to the extent of cancer: 80% (8 of 10) with Stage I, 66% (2 of 3) with Stage II, 54% (6 of 11) with localized Stage III, and 33% (4 of 12) with widespread Stage III were LAI positive. Leukocytes from patients with epidermoid, adenocarcinoma, or small cell lung cancer reacted to a common tumor antigen shared by extracts of epidermoid and small cell lung cancer. This study with coded samples from a remote hospital confirms the results of other investigators that the LAI measures an antitumor immune response to human organ-specific neoantigens.

Adenocarcinoma↗