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Biomedical subjects

N H Gordon

Publications and source records attributed to N H Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1992

Primary tumor size. Relevance to breast cancer survival.

In view of current emphasis on identifying prognostic factors for patients with early breast cancer, we studied the importance of tumor size to survival among 1392 patients with primary operable breast cancer who were followed up prospectively. All patients had modified radical mastectomies. Nine hundred seventeen patients had negative nodes and did not receive postoperative adjuvant therapy. Four hundred seventy-five patients had node involvement and received combination chemoendocrine therapy. In a Cox's proportional hazards model, tumor size was a significant predictor of disease-free and overall survival when the number of positive nodes, estrogen receptor status, menopausal status, and race were considered. Among the node-negative group, tumor size explained considerable variation in disease-free and overall survival, varying from a 10-year disease-free and overall survival of 80% and 99% for patients with estrogen receptor-positive tumors measuring 1 cm or less to a 10-year disease-free and overall survival of 51% and 59% for patients with tumors larger than 5 cm.

Aged↗
PubMed1992

Using toxicity grades in the design and analysis of cancer phase I clinical trials.

Ethical considerations in a cancer phase I trial require a design allowing determination of the maximum tolerated dose with a minimum number of patients treated at low ineffectual or high overly toxic doses. It would also be advantageous to complete the phase I trial in as short a period of time and with as few patients as possible to allow further resources for later studies in which patients are treated at the optimal dose. Several dose escalation schemes are compared. These are the Fibonacci, two two-stage schemes, and a proposed scheme which uses knowledge of all toxicity grades. Estimates of the maximum tolerated dose are obtained and compared using the dose escalation schemes alone, a logit model, and a proposed mean response model. Confidence intervals using the delta method are obtained from the logit and mean response models. The proposed scheme and the two-stage schemes have the advantage of requiring fewer patients, particularly at low doses. Confidence intervals obtained from the mean response model have better coverage than those from the logit model. Data from a cancer phase I trial of dipyridamole and acivicin is presented to illustrate the methods.

Antineoplastic Agents↗
PubMed1991

Local-regional breast cancer recurrence following mastectomy.

Local-regional recurrence patterns were investigated in 1392 patients with breast cancer. Primary treatment for all patients included a mastectomy. Nine hundred seventeen patients had negative nodes and did not receive systemic therapy. Four hundred seventy-five patients had node metastases and were randomized to receive different combinations of chemoendocrine therapy. Follow-up ranged between 5 and 16 years. Two hundred thirty (25.8%) node-negative patients have had recurrences, with the initial recurrence being local-regional in 9.2%. Two hundred forty-two (50.9%) node-positive patients have had recurrences, with the initial recurrence being local-regional in 17.1%. Larger tumors and more extensive node involvement were associated with more first local-regional recurrences. The relative percent of first local-regional recurrence among patients in whom cancer recurred was similar for node-negative and node-positive patients (35.4% and 33.5%, respectively). In 63.6% of patients in whom cancer recurred, first local-regional recurrence were distant. Larger tumors, more extensive node involvement, and a shorter disease-free interval after mastectomy were associated with more rapid appearance of distant recurrence among these patients.

Breast Neoplasms↗
PubMed1991

A critical analysis of the largest reported mass fecal occult blood screening program in the United States.

Fecal occult blood testing for the detection of colon cancer remains controversial. We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time. A total of 5,000 primary practitioners were notified by mail. Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned. Ninety-five percent of the respondents were informed of the program by television. A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up. Information from physicians regarding work-ups was returned on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed. Thirty-six colorectal cancers and 212 polyps were identified. The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade. Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up. Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant. Thirty-six percent of the tumors were located in either the right or transverse colon. We conclude that: (1) Screening identified early cancers. All were potentially curable and 64% were limited to the bowel wall. (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low. (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education.

Adult↗
PubMed1991

Estrogen receptor determination and long term survival of patients with carcinoma of the breast.

To investigate whether or not hormone receptor determination gives independent prognostic information for long term survival of patients with carcinoma of the breast, we studied 1,392 patients with early carcinoma of the breast. Patients were part of two prospective, multi-institutional trials, the first begun in 1974 and the second in 1980. Estrogen receptor assays were performed on all primary specimens taken of the carcinoma of the breast. Initial treatment for all patients was a modified radical mastectomy. Nine hundred and seventeen patients had negative axillary nodes and were observed without additional therapy. Four hundred and seventy-five had positive nodes and were randomized to receive combination chemoendocrine adjuvant therapy. One thousand and sixty-three (76.4 per cent) of the patients were found to have estrogen receptor positive (ER+) tumors (greater than or equal to 3 femtomoles per milligram cytosol of protein). The ten year over-all survival rate of 65.9 per cent was significantly better than that of 329 (23.6 per cent) patients with estrogen receptor negative (ER-) tumors (less than 3 femtomoles per milligram cytosol protein), who had a ten year over-all survival rate of 56.0 per cent (p = 0.0001). Higher estrogen receptor values were associated with Caucasian (p = 0.0001) and postmenopausal patients (p = 0.0001). In a proportional hazards regression model, patients with ER+ tumors had a significantly longer over-all survival period (p = 0.0001), but only a marginally improved disease-free survival time (p = 0.07) when compared with patients who had ER- tumors. These results indicate that ER determination does have prognostic value for long term over-all survival of patients with carcinoma of the breast. The greater importance of ER analysis to over-all compared with disease-free survival may be related to more easily managed recurrent disease among the ER+ group.

Aged↗
PubMed1990

Application of the theory of finite mixtures for the estimation of 'cure' rates of treated cancer patients.

I assume the survival function of treated cancer patients to be a mixture of two subpopulations, with c equal to the proportion who will die of other causes, and 1--c the proportion who will die of their disease. Using census data, I estimate the parameters of the survival distribution of those patients dying of other causes, and then use follow-up data to determine the maximum likelihood estimates of the proportion constant c and the parameters of the survival function of those dying of their disease. I illustrate the methodology using data from a prospective clinical trial in breast cancer.

Adult↗
PubMed1990

Modulation of tissue responsiveness to angiotensin-II in hyperprolactinemic subjects.

The present studies were designed to test the hypothesis that hyperprolactinemia modulates target tissue responsiveness to angiotensin-II (AII). Adrenal and pressor responses to AII infusions were determined in six patients with PRL-secreting pituitary microadenomas and in five normal controls during defined electrolyte balance. Hyperprolactinemic and normal subjects had similar mean blood pressures while on a regular Na intake (82.5 +/- 0.5 vs. 81.2 +/- 0.3 mm Hg). However, after 4 days of Na loading (200 meq/day), the mean blood pressure in hyperprolactinemic subjects was higher than that in normal (86.6 +/- 1 vs. 83.4 +/- 0.8 mm Hg; P less than 0.05). In addition, enhancement of the mean blood pressure response to three doses of AII was noted in hyperprolactinemic subjects (P less than 0.05) compared to that in normal subjects. After 4 days of Na restriction (10 meq/day), the mean blood pressure in hyperprolactinemic subjects was similar to that in normal subjects (79.7 +/- 0.6 vs. 78.9 +/- 1 mm Hg). However, despite adequate Na restriction, the pressor response to AII continued to be enhanced (P less than 0.05) in hyperprolactinemic subjects. There were no differences in plasma or urinary electrolytes or in PRA between hyperprolactinemic and normal subjects. Hyperprolactinemic subjects had higher basal (P less than 0.01), AII-stimulated (P less than 0.05), and ACTH-stimulated (P less than 0.02) aldosterone levels during Na loading, but not during Na restriction. The differences disappeared after the correction of the hyperprolactinemia. The data demonstrate significant alterations in adrenal and pressor responsiveness in hyperprolactinemic subjects and suggest a modulating role for PRL on vascular reactivity and steroid biosynthesis. The precise mechanism has not been determined, but may be secondary to PRL-induced up-regulation of adrenal and vascular AII receptors.

Adenoma↗
PubMed1990

Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer.

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.

Antineoplastic Agents↗
PubMed1990

A comparison of postoperative pain relief techniques in orchidopexy.

Fifty consecutive patients admitted to the Western General Hospital for orchidopexy, were randomly allocated to receive either a caudal bupivacaine block or peroperative wound instillation with bupivacaine, to provide postoperative analgesia. Bupivacaine wound instillation reduced the total operating time, gave more efficient postoperative pain relief in hospital and proved both inexpensive and simple in its application.

Adolescent↗
PubMed1989

Endocrine versus endocrine plus five-drug chemotherapy in postmenopausal women with stage II estrogen receptor-positive breast cancer.

Postmenopausal women who underwent modified radical mastectomy for Stage II, estrogen receptor (ER)-positive breast cancer were randomized to receive endocrine treatment (tamoxifen [T], 40 mg daily for 3 years) alone versus endocrine treatment plus five-drug chemotherapy (Cytoxan [cyclophosphamide, C], methotrexate [M], 5-fluorouracil [F], vincristine [V], and prednisone [P], CMFVP, for 1 year). Chemotherapy consisted of oral P (1 month), oral C (12 months), and intravenous MFV weekly for the first 3 months, biweekly for 3 months, and triweekly for 6 months. Patients were entered into the study from October 1979, to October 1985, and the median follow-up is 55 months. Results show that with 94 postmenopausal women, disease-free survival (DFS) is significantly greater (P = 0.04, log-rank test; P = 0.03, multivariate analysis) in patients receiving CMFVPT as compared to those receiving T alone. These results suggest that intensive chemotherapy combined with T is more effective in delaying recurrence than T alone in postmenopausal patients.

Aged↗
PubMed1989

Breast cancer survival and perioperative blood transfusion.

The effect of perioperative blood transfusion on disease-free and overall survival was studied in 812 patients with stages I and II breast cancer, followed up prospectively in a multicenter study. All patients initially underwent a modified radical mastectomy. Patients with axillary node-negative, stage I cancer were followed up without additional therapy. Patients with axillary node-positive, stage II cancer were randomized to receive adjuvant chemoendocrine therapy. Transfusion was done in 35.8% of the patients with stage I and in 37.3% of the patients with stage II cancer. For the patients with stage II cancer, perioperative blood transfusion did not affect disease-free or overall survival. For the patients with stage I cancer, perioperative blood transfusion resulted in a worse disease-free and overall survival (p = 0.05 and 0.02, respectively), which was particularly evident for those patients who received more than 1 unit. This study suggests that stage of disease, adjuvant therapy, number of transfusions, and duration of follow-up must be considered in further analyses.

Actuarial Analysis↗
PubMed1987

Recurrence patterns in a prospective study of patients with stage II breast cancer treated with endocrine-chemotherapy.

Local-regional versus distant recurrence patterns were investigated for 311 patients with stage II node-positive breast cancer who were part of an endocrine-chemotherapy adjuvant breast cancer trial. After mastectomy patients were randomized to receive either cytoxan, methotrexate, and 5-fluorouracil (CMF) (1 year) or CMF with tamoxifen (1 year) with or without bacillus Calmette-Guérin (BCG). With a median follow-up of 92.1 months, 55.3% of the patients had recurrences. The first site of recurrence was local-regional for 31.4% of patients and distant for 68.6%. This pattern of first recurrence was not associated with treatment groups, menopausal status, race, estrogen receptor value, number of positive lymph nodes, or tumour diameter. Although patients with a first local-regional recurrence had a better overall prognosis compared with those with a first distant recurrence, 52.2% of those patients with an initial local-regional recurrence developed a distant recurrence within 12 months. Among patients who had a recurrence, 48.3% had a local-regional recurrence at some time during their follow-up. Conclusions from this study are (1) patterns of recurrence were not affected by the addition of antiestrogen therapy to chemotherapy; (2) for the variables tested, including number of positive nodes and tumor diameter, no association with recurrence patterns was found; and (3) most patients (52.2%) with a first local-regional recurrence will develop a distant recurrence within 1 year.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Assessment of tamoxifen as adjuvant therapy in stage II breast cancer: a long-term follow-up.

Results of a prospective, randomized clinical trial of three treatment regimens--cyclophosphamide, methotrexate, and 5-fluorouracil (C); C plus the antiestrogen, tamoxifen citrate (CT); and CT plus bacillus Calmette-Guerin (CTBCG)--in 311 women with stage II breast cancer are reported. The data were analyzed by univariate (product limit and log rank) analysis and by multivariate analysis. Estrogen receptors were measured in all primary tumors. The mean follow-up period was 78.2 months. The regimens containing tamoxifen citrate significantly decreased the risk of recurrence in patients with positive estrogen receptors. The addition of tamoxifen does not, however, appear to provide an advantage in overall survival. No benefit in disease-free or overall survival was observed resulting from the addition of BCG to the treatment regimen. The design of the study did not permit an evaluation of the efficacy of the chemotherapy used inasmuch as all patients received it.

Analysis of Variance↗
PubMed1986

Influence of tamoxifen and estradiol on the growth of human breast cancer cells in vitro.

Cells obtained from freshly resected human breast cancer were grown in vitro utilizing the soft agar technique. The effects of adding an antiestrogen (tamoxifen, TAM) and 17 beta-estradiol alone or simultaneously on cell growth were assessed. The addition of TAM (10(-6) M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%). The degree of inhibition caused by TAM was significantly higher in the ER-positive tumors that also contain the progesterone receptor (PgR) as compared to those that lacked that receptor (i.e., PgR negative) (46.2 +/- 2% versus 36.2 +/- 1.2% inhibition, P less than 0.01). The simultaneous addition of 17 beta-estradiol (10(-8) M) neutralized the inhibitory effect of TAM (10(-6) M) in the majority of tumors. With the presence of serum in the medium, the addition of 17 beta-estradiol alone resulted in an enhancement of cell growth in 6 of 17 tumors. However, because of the confounding effects of serum in the medium, we studied the individual effect of 17 beta-estradiol (10(-8) M) when added alone under serum-free conditions. Of 20 tumors studied, 17 beta-estradiol significantly enhanced cell growth in 12. There was a 67.8 +/- 12.6% increase in the number of colonies formed in these 12 responding tumors. One of these 12 responding tumors was ER negative as well as PgR negative, while the rest were all ER positive. These in vitro studies demonstrate that this approach can provide valuable information on endocrine mechanisms controlling the growth of human breast cancer.

Breast Neoplasms↗
PubMed1986

The influence of tibial-patellofemoral location on function of the knee in patients with the posterior stabilized condylar knee prosthesis.

Function of the knee and patellofemoral symptoms were correlated with the position of the implant in 101 consecutive patients with 116 posterior stabilized condylar knee prostheses. All of the patients were followed for a minimum of two and a half years with sequential physical examinations, radiographs, and functional evaluation of the knee. In sixteen knees (14 per cent), clicking or catching of the patella in terminal extension or painless crepitation throughout the arc of flexion developed without lowering the functional knee-evaluation score. Pain or mechanical problems, or both, that lowered the functional knee-evaluation score occurred in another fourteen knees (12 per cent), within the first postoperative year. Of these fourteen, eight required revision solely for patellofemoral complaints. Critical analysis of the tibial-patellofemoral mechanical axis identified three surgical variables that were found to markedly affect the functional result of the prosthesis: the distance from the center line of the tibial prosthesis to the center line of the tibial plateau, a change in the position of the joint line of the prosthesis relative to the hip and ankle, and the patellar height, measured as the perpendicular distance from the inferior pole of the patellar implant to the joint line of the prosthesis. Functional knee scores, range of motion, patellofemoral pain or mechanical symptoms, the need for revision, and the necessity of manipulation could all be statistically significantly correlated with the three independent variables. In addition, a range of neutral alignment was developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The interaction of estrogen receptor status and race in predicting prognosis for stage I breast cancer patients.

As part of a multi-institutional breast cancer data base, 501 stage I, node negative patients have been followed prospectively with a median of 89 months. Patients were treated by a modified radical mastectomy without postoperative therapy. Estrogen receptor (ER) content of the primary tumor was determined in all cases. For the entire patient group at 10 years, the disease-free survival (DFS) rate is 72% and the overall survival (OS) rate is 85%. Both ER value and race (black versus white) were found to be significant prognostic variables for DFS (p = 0.008 and 0.02, respectively) and for OS (p = 0.0001 and 0.01, respectively). ER positive patients had a better DFS and OS rate compared with ER negative patients (74% versus 66% and 90% versus 68%, respectively). Black patients had significantly worse DFS and OS rates compared with white patients (64% versus 74% and 75% versus 86%, respectively). Statistical interaction between the ER and race variables was apparent when comparing the similar DFS for ER positive white (75%), ER negative white (72%), and ER positive black (73%) patients in contrast to a DFS of less than 42% at 10 years for the ER negative black patients. An analysis of the data for the ER negative black patients suggested that the postmenopausal ER negative black patients are at particularly high risk of recurrence and death from breast cancer.

Breast Neoplasms↗