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Biomedical subjects

D R McCready

Publications and source records attributed to D R McCready.

At least 37 records · Page 2Linked to original sources
PubMed1996

Factors associated with local breast cancer recurrence after lumpectomy alone.

BACKGROUND: The purpose was to determine the rate of local breast relapse in patients with breast cancer uniformly treated with partial mastectomy but without postoperative radiotherapy and without systemic adjuvant therapy. We also systematically examined the factors associated with local recurrence to determine whether a low-risk subgroup existed. METHODS: A retrospective review of a prospectively followed (median, 8 years) cohort of 293 patients was performed. The end-point was ipsilateral local breast cancer recurrence. The patient's age, tumor size, nodal status, estrogen and progesterone receptor status, histology, and tumor and nuclear grade were studied, as were the presence and amount of carcinoma in situ and the presence of tumor emboli using univariate Kaplan-Meier and Cox step-wise multivariate analyses. RESULTS: The overall local relapse rate was 26% (77 recurrences). Univariate factors significantly associated with decreased local relapse included older age, negative nodes, small tumor size, positive estrogen receptor status, and absence of tumor emboli. Significant multivariate variables were age, nodal status, estrogen receptor status, absence of comedo carcinoma in situ, and tumor emboli. A low-risk subgroup of 66 patients was defined with a 6% 10-year local recurrence rate. CONCLUSION: Important patient and tumor variables associated with local breast cancer relapse after breast-conserving surgery can define a low-risk subgroup.

Adult↗
PubMed1996

An improved statistical approach: can it clarify the role of new prognostic factors for breast cancer?

Recently, there has been a proliferation of new biomarkers, some of which may lead to an improved prognostic index or may influence treatment selection. However, there are methodological and statistical issues that require attention in assessing the role and use of these prognostic factors. Between 1977 and 1986, 1097 primary breast cancer patients were accrued for multidisciplinary research at the Henrietta Banting Breast Centre, Women's College Hospital; follow-up to 1990 is complete for 96% of the patients. Data for these patients are used here to illustrate strategies: (1) for the comparison of results from diverse assessments of biomarkers; (2) for the improved comparability of inter-laboratory results; (3) for the examination of the results from monoclonal or polyclonal antibody assays for possible clinically relevant bimodality; (4) for good statistical resolution of overlapping distributions; (5) that involve the use of quantitative values for prognostic factors whenever possible; and (6) for improved multivariate analyses. Good data handling and analyses may enable more accurate and rapid assessment of new prognostic factors, thereby expediting and improving their clinical application.

Analysis of Variance↗
PubMed1996

An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays.

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from - 1.0 to + 1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.

Breast Neoplasms↗
PubMed1996

Combined fine-needle aspiration, physical examination and mammography in the diagnosis of palpable breast masses: their relation to outcome for women with primary breast cancer.

OBJECTIVE: To examine the combined and individual predictive values of fine-needle aspiration (FNA), physical examination (PE) of the breast and mammography (the "triple test") in diagnosing breast cancer in relation to the results of open surgical biopsy. DESIGN: A study of the records of patients who received both FNA and open surgical biopsy for the same palpable breast lump. The results of diagnostic assessment and open surgical biopsy were categorized as positive or negative. Concordance (percentage of tests found to be correct at biopsy), sensitivity, specificity (percentage of patients without breast cancer for whom the diagnostic test was negative) and positive predictive value (percentage of patients with a positive test found to have breast cancer) were determined for the triple test for each diagnostic modality. In addition, prognostic variables (tumour size, node positivity, estrogen and progesterone receptor status) and outcomes were assessed in patients with a diagnosis of breast cancer. SETTING: A university-affiliated general hospital with a special focus on women's health. PATIENTS: Of 290 patients who had both FNA and open surgical biopsy, 191 underwent all three diagnostic procedures. MAIN OUTCOME MEASURES: The diagnostic accuracy of FNA, PE and mammography to permit preoperative definitive therapy or to allow observation without mandating open surgical biopsy. RESULTS: In 81 patients all three diagnostic modalities were in agreement for a diagnosis of either benign or malignant disease; the concordance for the triple test was 98.8% specificity was 100% and sensitivity was 95.5%. Nodal status, tumour size and outcome were similar whether or not the triple test was positive, but, interestingly, when the triple-test results were positive, estrogen (p < 0.05) and progesterone (p < 0.03) receptor values were more likely to be negative. CONCLUSIONS: When all three diagnostic modalities were in agreement for a diagnosis of malignant disease, the combination of FNA, PE and mammography had excellent concordance with the results of open surgical biopsy, and in this situation definitive treatment may be carried out. If all three modalities are in agreement for a diagnosis of benign disease, a period of close observation with repetition of FNA may be safely entertained. Lack of concordance of the three diagnostic modalities mandates biopsy. Triple-test positively does not predict a worse outcome.

Adult↗
PubMed1994

Characteristics of local recurrence following lumpectomy for breast cancer.

We report the clinical characteristics and treatment of local breast relapse in our breast cancer patients who were initially managed with breast conservation surgery (lumpectomy) alone. A retrospective study was conducted of 366 patients who were treated since 1977. The clinical, pathological, and treatment data regarding the primary tumor and the recurrences (91) were reviewed. The actuarial rate of local breast relapse in this group was 31% at 10 years. Breast relapse was significantly less in those patients 65 years old or greater. Acceptable treatment of the breast relapse included total mastectomy or repeat lumpectomy plus radiotherapy. Most relapses were small and occurred in the same area as the original tumor and had similar histology and estrogen and progesterone receptor values. About one-third of patients will have isolated relapses after conservation surgery alone, but in the older age group, isolated breast relapse occurs less frequently. The recurrences are usually surgically resectable, and acceptable results can be achieved with salvage surgery.

Aged↗
PubMed1992

A comparison of all-subset Cox and accelerated failure time models with Cox step-wise regression for node-positive breast cancer.

Clinical studies usually employ Cox step-wise regression for multivariate investigations of prognostic factors. However, commercial packages now allow the consideration of accelerated failure time models (exponential, Weibull, log logistic, and log normal), if the underlying Cox assumption of proportional hazards is inappropriate. All-subset regressions are feasible for all these models. We studied a group of 378 node positive primary breast cancer patients accrued at the Henrietta Banting Breast Centre of Women's College Hospital, University of Toronto, between January 1, 1977, and December 31, 1986. 85% of these patients had complete prognostic factor data for multivariate analysis, and 96% of the patients were followed to 1990. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, number of positive nodes and adjuvant systemic therapy. The data strongly supported the log normal model. The all-subset regressions indicated that three models were similarly good. The variables 1) number of positive nodes, 2) tumour size, and 3) adjuvant systemic therapy were included in all three models along with one of three biochemical receptor variables 1) ER, 2) combined receptor (ER- PgR-; ER+PgR-; ER- PgR+; ER+PgR+; or 3) PgR. Better multivariate modeling was achieved by using quantitative prognostic factors, a check for appropriate underlying model-type, and all-subset variable selection. All-subset regressions should be considered for routine use with the many new prognostic factors currently under evaluation; it is very possible that there may not be a single model that is substantially better than others with the same number of variables.

Adult↗
PubMed1992

Total mastectomy is not always mandatory for the treatment of recurrent breast cancer after lumpectomy alone.

To determine the treatment that offered the best local control for isolated local recurrences of breast cancer after lumpectomy without radiotherapy, the authors reviewed 355 patients initially treated by lumpectomy (with or without axillary dissection) without radiotherapy. Local breast cancer recurred in 79 patients. They underwent either repeat partial mastectomy (PM) or completion total mastectomy (TM). Twenty-four patients (5 TM, 19 PM) received radiotherapy. Local control was defined as the absence of further recurrence of breast or chest-wall cancer. The 19 patients treated with repeat PM and radiotherapy had an actuarial local control rate of 82% at 5 years. Those treated with TM (28 patients) [corrected] or TM plus radiation (5 patients) had rates of local control of 60% and 52% respectively. Although there were no significant differences between the TM and PM plus radiotherapy groups, the 27 patients who had a repeat PM without radiotherapy had a significantly lower rate of local control (32%, p < 0.005). Treatment of recurrent breast cancer with PM and radiotherapy is a viable alternative to TM for enhancing local control. Repeat PM alone gave much poorer results. The authors conclude that local cancer recurrences after lumpectomy alone do not necessarily require TM and can often be treated with repeat excision and radiotherapy.

Adult↗
PubMed1990

Outpatient percutaneous central venous access in cancer patients.

A 1-year experience of percutaneous subclavian catheterization in outpatients with cancer was reviewed to document reliability, safety, and cost. There were 763 catheter insertions attempted with prospective documentation of complications in 664 consecutive patients. Catheter insertion was successful in 722 attempts (95%). There were only 13 pneumothoraces (2%). Thirty catheters required repositioning (4%). The average catheter duration was 191 days (range: 0 to 892 days). Fifty-six catheters (8%) were removed because of suspected infection. Documented catheter sepsis occurred in 21 patients (3%); catheter site infection occurred in 8 patients (1%). Thus, only 0.22 infections per catheter year occurred during this 382 catheter-year experience. The estimated cost of catheter insertion was $562, which is one-third the estimated cost for tunneled catheters ($1,403) and for reservoir devices ($1,738). In our experience, percutaneous subclavian catheterization is a reliable, cost-effective method compared with tunneled or reservoir devices, with an equivalent incidence of catheter-related infections. The cornerstone of our success with this program is a staff dedicated to catheter care and intensive patient education. In centers where a large number of patients require central venous access, percutaneous catheterization should be the technique of choice.

Ambulatory Care↗
PubMed1989

Lack of comparability between binding of monoclonal antibodies to melanoma cells in vitro and localization in vivo.

The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors.

Animals↗
PubMed1989

The prognostic significance of lymph node metastases after preoperative chemotherapy for locally advanced breast cancer.

We compared the prognostic value of surgical lymph node staging after preoperative chemotherapy relative to other patient and tumor variables in 136 patients with locally advanced breast cancer (T3-4 and/or N2-3) who received preoperative chemotherapy followed by mastectomy and axillary dissection as part of a prospective protocol. Univariate analysis revealed that the number of metastatic lymph nodes, clinical tumor stage at presentation, clinical and pathologic response, and menopause status were significant variables associated with survival and disease-free survival, but clinical node stage at presentation and estrogen receptor status were not. The number of metastatic lymph nodes had more prognostic value than the other factors, and when evaluated by multivariate regression, surgical node staging added significantly more information to the remaining variables. Surgical staging is an important component of treatment for patients with breast cancer undergoing preoperative chemotherapy because it can provide an accurate and quantitative method for subgrouping patients with different survival rates and it can be used to compare results between preoperative chemotherapy trials.

Adult↗
PubMed1989

Prospective phase I trial of conservative management of low rectal lesions.

The purpose of this study was to assess and function and to compare the morbidity of local excision and postoperative radiotherapy for rectal adenocarcinoma with the morbidity of abdominoperineal resection. A posterior parasacral approach was used for local excision. All patients had negative margins, and all but one were continent after completion of radiotherapy. Seven patients (29%) had either a wound infection or a fistula in the local excision group. No local failures occurred, although follow-up was only 13 months. Thirteen (50%) of the 26 patients who underwent an abdominoperineal resection developed at least one complication. Combined treatment that spares the rectal sphincters may be preferable in selected patients with low rectal cancer, if long-term disease-free survival is maintained.

Adenocarcinoma↗
PubMed1989

Altered biodistribution of indium-111-labeled monoclonal antibody 96.5 to tumors and normal tissues of nude mice bearing human melanoma xenografts in visceral organs.

Human melanoma xenografts were produced in the subcutis, kidney, cecum and liver of different nude mice. An 111In-labeled anti-(human melanoma) monoclonal antibody (96.5) or an 111In-labeled nonspecific control monoclonal antibody (ZCE-025) was injected intravenously in separate groups of mice. Radioactive antibody accumulation was measured in tumor, blood, viscera, and carcasses. mAb 96.5 targeted specifically to tumor tissue regardless of site of growth. Tumors in the liver exhibited significantly (P less than 0.05) higher tumor-to-blood ratios (45 +/- 6, mean +/- SEM) than xenografts at other visceral organs, the lowest value being found for subcutaneous melanoma (2.6 +/- 0.5). The differences in tumor-to-blood ratio were due to significant alterations of antibody biodistribution, since the actual antibody concentration in the different tumor sites was similar. The percentage of recovered anti-melanoma antibody per milliliter of blood in mice with visceral lesions (4.6 +/- 1.1% ml) was significantly lower than that found in mice with subcutaneous tumors (9.5 +/- 1.4%/ml, P less than 0.05). Moreover, significantly higher levels (18.2 +/- 3.2%/g, 31.0 +/- 5.1%/g, respectively) of the melanoma mAb 96.5 were found in normal liver and spleen tissue recovered from mice with visceral tumors as compared to tissue from mice with subcutaneous tumors (9.2 +/- 0.9%/g, 13.5 +/- 1.9%/g, respectively; P less than 0.05). These results demonstrate that the presence of visceral tumor can significantly affect tumor-to-blood ratios, blood levels, and biodistribution of 111In-labeled mAb 96.5.

Animals↗
PubMed1985

Protection against aspirin-induced antral and duodenal damage with enprostil. A double-blind endoscopic study.

Prostaglandins protect against aspirin-induced damage to the gastrointestinal tract. This study tested the ability of enprostil, a synthetic analog of prostaglandin E2, given concurrently to prevent gastroduodenal injury. Twenty-four healthy subjects were randomly assigned to one of three groups. All received aspirin 650 mg q.i.d. for 5 days. One group received placebo and the other groups were given either 7 or 70 micrograms of enprostil b.i.d. for 5 days. Upper endoscopy was performed at entry and 2 h after the final dose of aspirin. Enprostil 70 micrograms b.i.d. afforded significant protection of both the antral and duodenal mucosa. The 7-micrograms dose protected only the antral mucosa. Side effects were not observed with the lower dose of enprostil. Serum salicylate levels did not differ significantly between the groups.

Adolescent↗
PubMed1985

Cigarette smoking reduces human gastric luminal prostaglandin E2.

The effect of smoking three cigarettes on the release of prostaglandin E2 (PGE2) by the gastric mucosa was studied in seven healthy smokers. Smoking caused the expected increases in pulse rate, blood pressure, plasma glucose, and carboxyhaemoglobin. In addition, smoking resulted in a significant (p less than 0.05) reduction in the volume of pentagastrin stimulated gastric juice from 76.1 +/- 4.4 to 54.1 +/- 4.6 ml/15 min and PGE2 output from 22.8 +/- 4.9 to 12.2 +/- 3.8 ng/15 min but did not alter acid output. It is concluded that smoking reduces the amount of PGE2 in the gastric lumen and that this may explain why it is a risk factor for peptic ulcer.

Adult↗
PubMed1984

Prostaglandin biosynthesis by gastric mucosa. I. Studies in rat.

A technique for determination of the prostaglandin E2 biosynthetic capacity ( PGBC ) of gastric mucosa is described. The effects of food deprivation and indomethacin pretreatment on PGBC were studied. Indomethacin (1 mg/kg i.p.) significantly reduced the PGBC of fundal and antral tissue. This effect was more marked in the fundal tissue. Food deprivation for up to 22 h had no effect on fundal PGBC . In the antrum, a 12-hour fast caused a significant reduction in PGBC while a 22-hour fast had no effect. These changes in PGBC may relate to the increase in susceptibility to gastric ulceration caused by fasting or indomethacin pretreatment. This technique may be applicable to clinical studies.

Animals↗
PubMed1984

Prostaglandin biosynthesis by gastric mucosa. II. Studies in man.

The concentration of prostaglandin E2 (PGE2) in gastric juice and the PGE2 biosynthetic capacity ( PGBC ) of mucosal biopsies were studied before and after a five-day course of acetylsalicylic acid (650 mg QID) in seven healthy subjects. Gastric juice PGE2 concentration varied between individuals, but mucosal PGBC was relatively constant. After the five-day course of acetylsalicylic acid both measurements were significantly lower. PGE2 concentration fell 49 +/- 8% and PGBC was reduced by at least 97%. The ready availability of these samples at endoscopy and the sensitivity and reproducibility of the measurements suggest that these techniques may be valuable in clinical studies of gastric function and disease.

Adult↗