Search PubMed⌕ Search

Biomedical subjects

W A Knight

Publications and source records attributed to W A Knight.

At least 37 records · Page 2Linked to original sources

Multiple estrogen receptor assays in human breast cancer.

A review of assay results from more than 6000 patients revealed 232 patients in whom multiple breast cancer specimens were analyzed for estrogen receptor (ER). All assays were performed in a single laboratory. Specimens were considered estrogen receptor positive (ER+) if the ER level was greater than 10 fmol/mg protein and estrogen receptor negative (ER-) if the ER level was less than 3. ER values between 3 and 10 fmol/mg protein were considered borderline. Simultaneous assays were performed in 58 patients with 3% major discordance (i.e., one assay ER- and one assay ER+). Major discordance for sequential biopsies was 19% (16 of 82) when the initial assay was ER+ and 13% (eight of 63) when the initial assay was ER-. (Apparent change from ER- to ER+ status was observed in five of nine patients with primary tumors less than 2 cm in diameter, suggesting that an inadequate amount of tissue may have been submitted for initial ER analysis.) There was no significant relationship between the time interval between sequential biopsies and the rate of discordance. Marked decreases in ER levels and 78% discordance were seen if rebiopsy was performed within 2 months of tamoxifen treatment. When these tamoxifen cases were excluded from the analysis, neither intervening endocrine therapy nor chemotherapy significantly altered discordance rates.

Adult↗

Elevation of serum amylase levels after narcotic administration.

Hyperamylasemia after narcotic administration is found in some patients. To determine the source of the amylase, serum isoamylases were separated by column chromatography in a group of patients with response to a Prostigmin-morphine challenge. The increment of amylase activity was pancreatic amylase.

Adult↗

Steroid hormone receptors and carcinoma of the breast.

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50-60% are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of subsequent relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of ER and assay of progesterone receptor (PgR) are useful for increasing the accuracy of selecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be the best available tumor marker of hormone dependence.

Adolescent↗

Adjuvant therapy for stage II, estrogen receptor negative breast cancer.

The estrogen receptor (ER) assay provides information which correlates with the proliferative potential, pathology and prognosis for patients with breast cancer. A review of our natural history data correlating ER and axillary node involvement at the time of mastectomy with prognosis allows the identification of a high risk subset of patients with early recurrence and poor survival. Patients with ER negative, stage II disease had a significantly higher recurrence rate, and poorer overall survival was observed in spite of systemic therapy instituted at relapse. Based on this data we initiated a pilot study of intensive adjuvant therapy for women with ER negative, stage II breast cancer. At a median follow-up of 19 months for 39 treated patients, both a disease free and overall survival advantage is apparent for treated patients. Morbidity was low, with no therapy related hospitalizations. We have demonstrated the feasibility of intensive therapy for this high risk group. For a definitive answer the patient resources of a cooperative group will be needed.

Actuarial Analysis↗

Correlation of primary breast cancer histopathology and estrogen receptor content.

We studied the association of estrogen receptor (ER) with several histologic variables that correlate with breast tumor differentiation and with patient prognosis. Contingency table analysis revealed highly statistically significant correlations between ER content and histologic and nuclear grades, tumor necrosis, and the degree of elastosis and lymphoid cell infiltration. ER positive tumors were more likely than ER negative tumors to demonstrate histological evidence of tumor differentiation. All tumors with histologic grade 1 or nuclear grade 1 (best differentiated) were ER positive or borderline positive. Eighty-nine percent of ER negative tumors were histologic grade 3 and 78.4% were nuclear grade 3 (poor differentiation). ER positive tumors were also correlated with absent tumor necrosis, higher elastic content, and absent lymphoid cell infiltration, all features of good differentiation. Medullary carcinomas were frequently (73%) ER negative, but no relationship between ER and other morphologic types of breast cancer or 9 other morphologic variables was found. ER appears to be a biochemical marker for the degree of differentiation of human breast cancer providing a rationale for the observed differences in biological behavior between receptor positive and negative tumors.

Axilla↗

Phase I-II trial of methyl-GAG in advanced colon cancer. a Southwest Oncology Group pilot study.

Forty-four patients with advanced colon or rectal cancer were treated with methyl-GAG on a weekly schedule. Of the 40 evaluable patients, 35 (87%) had received prior chemotherapy. Objective tumor regression was seen in six patients (one CR, five PR's). An additional nine patients had stable disease for a median of 42 weeks. The median survival (42+ weeks) for responding and stable disease patients was significantly better (p = 0.0001 Wilcoxan test) than those with progressive disease (11 weeks). Toxicity was reversible and included mild to moderate mucositis, nausea, vomiting, diarrhea, and thrombocytopenia. Responses observed in this study warrant further trials in patients with colon cancer who have no prior chemotherapy.

Adult↗

The value of estrogen and progesterone receptors in the treatment of breast cancer.

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50 to 60 percent are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of clinical relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of Er and an assay for progesterone receptor (PgR) are two methods for increasing the accuracy of selecting or rejecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be a better marker of tumor hormone dependence than quantitative ER.

Breast Neoplasms↗

Hormone receptors in primary and advanced breast cancer.

The use of cytoplasmic ER is an integral part of the management of patients with metastatic breast cancer. Tissue from the primary tumour should be routinely assayed for ER and, when feasible, metastatic tissue should be obtained for assay. In addition, ER is an important prognostic variable for recurrence and overall survival and may be useful in the design of adjuvant therapy trials. Whether knowledge of receptor status correlates with chemotherapy response has yet to be conclusively determined. Whether PgR will ultimately add to the clinical usefulness of ER has also yet to be clearly defined; however, it is known that patients whose tumour contains both receptors have a high response rate to hormone therapy. These questions, and others await confirmation in prospective clinical trials.

Acute Disease↗

Steroid hormone receptors in the management of human breast cancer.

Recent insight into the mechanism of steroid hormone receptors in human breast cancer has led to new approaches in treatment strategy. Estrogen receptor (ER) has now replaced clinical criteria in the selection of patients for endocrine therapy. Patients whose tumors do not contain ER should not be subjected to hormonal manipulation. In addition, ER measured on the primary tumor has been found to be an independent prognostic factor for both recurrence and survival. Patients with ER negative primary tumors have a poorer prognosis. This information may be useful in the design and selection of therapy for future adjuvant clinical trials. In metastatic breast cancer, the absolute ER value may provide valuable information regarding endocrine responsiveness. In addition, the measurement of progesterone receptor (PgR) may provide additional insight for predicting with confidence those patients likely to respond.

Breast Neoplasms↗

Modern approaches to the treatment of breast cancer.

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.

Breast Neoplasms↗

Primary linitis plastica of the colon: report of two cases and review of the literature.

Two cases of primary linitis plastica of the large intestine will be presented and discussed. Characteristic clinical features of this type of adenocarcinoma of the large intestine include younger age of presentation, low incidence of hepatic metastasis and a high incidence of ovarian, lymph node and peritoneal metastasis. Pathological features reveal thickening of the intestinal wall by diffuse infiltrating tumor cells of the characteristic signet ring cells, abortive glands and undifferentiated or anaplastic cells. The prognosis is poor.

Adenocarcinoma, Mucinous↗

A simple assay technique for pancreatic lipase.

A simple and inexpensive procedure is described to include pancreatic lipase in the protocol for evaluation of pancreatic function by duodenal aspiration. The method involves dilution with an albumin solution, a 2-hr incubation with a commercially available substrate mixture, and manual titration with a burette. Results comparable to assay with a pH-stat were obtained. Assay for pancreatic lipase is recommended as a part of the diagnostic procedure of duodenal aspiration.

Adult↗

Inherited defect in hereditary pancreatitis.

Definite inherited defect in hereditary pancreatitis (HP) is not known. A new kindred with 3 definite and 6 suspected cases of HP was investigated for possible inherited abnormalities. No aminoaciduria (except for a slight rise in urinary histidine in one patient) and no hyperparathyroidism, hyperlipidemia, or chromosomal abnormality was present. An increase in serum IgM level of a polyclonal type was noted in 3 definitely affected sisters and also in 2 nonaffected members. Serum alpha-1-antitrypsin and serum trypsin inhibition were normal. However, very marked dilatation and ectasia of the pancreatic duct were found in the propositus. Reviewing the data from this family and previously described kindreds, it is postulated that the genetic abnormality in HP encompasses a wide variety of structural and anatomical defects in the sphincter of Oddi or the pancreatic ductal system. These predispose to intermittent obstruction of the duct with concomitant activation of enzymes and ductal metaplasia. In suspected cases an early effort should be made to outline the pancreatic duct as the defect may be amenable to surgery.

Adult↗