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Biomedical subjects

J P Minton

Publications and source records attributed to J P Minton.

At least 19 recordsLinked to original sources

The regional treatment of liver metastases from breast cancer.

To determine the effect of aggressive regional therapy for liver metastasis from breast cancer, we retrospectively reviewed data on 74 patients identified with liver metastases. Forty had only liver metastases. In this group of 40 patients, 18 were treated with regional therapy only, i.e., surgical resection and/or regional chemotherapy via hepatic artery or portal vein catheters whereas 22 patients had systemic chemotherapy. The two groups were comparable. The regional chemotherapy regimen was 5-FU, Adriamycin, methotrexate, and cytoxan. Median survival (27 months) for those patients treated with regional therapy (N = 18) was significantly longer than for those (N = 22) treated with systemic therapy (5 months) (P = 0.001). Only 45% of the regional treatment group failed in the liver. Our data, although retrospective and selective, suggest that certain subgroups of breast cancer patients with metastatic liver disease may benefit from aggressive regional therapy.

Adult↗

Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

PURPOSE: To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS). PATIENTS AND METHODS: Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP. RESULTS: The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone. CONCLUSION: CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.

Adult↗

One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study.

PURPOSE: To determine if prolonged adjuvant treatment (2 years v 1 year) with combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil [5-FU], vincristine, and prednisone [CMFVP]) in poor-prognosis breast cancer patients (estrogen receptor [ER]-negative, stage II to IIIA) would result in improved disease-free and overall survival rates. PATIENTS AND METHODS: Four hundred forty-five women with ER-negative node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) over a period of 5 years (1979 to 1984). Randomized assignments were made to either 1 or 2 years of adjuvant CMFVP. Doses were daily oral cyclophosphamide 60 mg/m2, intravenous (i.v.) weekly methotrexate 15 mg/m2, i.v. weekly 5-FU 400 mg/m2, i.v. weekly vincristine .625 mg/m2 for the first 10 weeks, and prednisone weeks 1 through 6 with doses decreasing from 30 mg/m2 to 10 mg/m2. RESULTS: The median follow-up duration is 8.6 years, with a maximum of 11.3 years. Treatment arms were not significantly different as regards either survival or disease-free survival rates (P = .33 and P = .24, respectively). The five-year survival rate is 57% on the 1-year arm and 62% on the 2-year arm. Patients with three or fewer nodes and premenopausal status were associated with improved survival. Compliance on the 2-year arm was poor, with only 37% completing the full 2 years of treatment. SWOG grade 3 to 4 toxicity was experienced by 47% of patients on the 1-year arm and by 52% on the 2-year arm. There were no treatment-related deaths. CONCLUSION: We conclude that 2-year adjuvant treatment with CMFVP is not an improvement over 1-year treatment. Moreover, 2 years of CMFVP is difficult to complete. However, the results are not definitely negative. A moderate improvement attributed to prolonged chemotherapy, especially among patients with four or more positive nodes, cannot be ruled out.

Adult↗

Low-dose cyclophosphamide enhances helper-to-non-helper ratios.

This study was conducted to analyze the effect of different doses of cyclophosphamide (CY) on the lymphocyte populations in the rat. Monoclonal antibodies against rat determinants were used: W3/13 (T lymphocytes), W3/25 (T helper), OX-8 (non-helper), and OX-33 (B lymphocytes). Blood samples were collected on days 0, 3, 7, and 14 from four groups of F-344 Fisher rats (n = 4): three that received 25, 50, or 75 mg/kg of CY and a control group. The duration and severity of lymphocyte depletion were dose-related and were evident for both helper and non-helper cells (p less than 0.02). The helper-to-non-helper ratio increased for the group that received 25 mg/kg when compared with control and other groups, but was only significantly changed when compared with the 75 mg/kg group (p = 0.004). This effect was transitory and was only seen on day 3. The control and the 25 mg/kg groups gained weight; the other two groups lost weight (p less than 0.05). Lower doses of CY were associated with a transitory immunostimulatory effect and no morbidity when compared with higher doses.

Adjuvants, Immunologic↗

Metastatic pheochromocytoma associated with multiple endocrine neoplasia syndrome type II.

Pheochromocytoma is a rare adrenal medullary tumor of chromaffin cell origin that presents a syndrome of alpha- and beta-adrenergic receptor stimulation due to secretion of epinephrine and norepinephrine. This tumor occurs sporadically in the population and is also associated with multiple endocrine neoplasia syndrome type II (MEN II). Although malignant pheochromocytoma is associated with sporadic tumors, those associated with familial MEN syndromes are rarely malignant. We report a case of a rare metastatic pheochromocytoma in a patient with MEN IIA. Surgical debulking, which has been shown to benefit many patients with metastatic neuroendocrine tumors, was attempted in this patient. Palliation, with symptom relief, was provided. The options for treatment of metastatic pheochromocytoma are discussed.

Adrenal Gland Neoplasms↗

Ablation of recurrent and metastatic intraabdominal tumor with the CO2 laser.

A retrospective study was carried out to determine the usefulness of the CO2 laser in the management of patients with recurrent and metastatic intraabdominal tumors. Twenty-six intraabdominal procedures utilizing the laser were carried out on 24 patients at The Ohio State University between 1984 and 1988. This included 11 patients with recurrent adenocarcinoma of colonic origin, 3 patients with malignant carcinoid tumors, 3 patients with ovarian carcinomas, and one patient each with metastatic pheochromocytoma, appendix, breast, stomach, and lung carcinoma. In addition, there was one patient with pseudomyxoma peritoneii and one patient with both colonic and ovarian carcinoma. Tumors were located in the retroperitoneum (3), pelvis (2), liver (11), bowel serosa (5), diaphragm (4), mesentery (3), and peritoneal implants (3). The laser was used as an adjunct to standard surgical techniques and in most instances was combined with other operative procedures. Its use was greatest in cases where en bloc resection was impossible, as with hepatic lesions located near the hepatic veins or vena cava. Additional benefit was derived in cases where cytoreductive or debulking surgery was useful as in ovarian carcinoma and metastatic neuroendocrine tumors. All four patients with neuroendocrine tumors are still alive 3, 7, 12, and 56 months after surgery. In addition, symptom relief was apparent in all after surgery. All patients with ovarian carcinoma are also alive 9-29 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast.

Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node ("skip") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor-involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer.

Adult↗

Carcinoembryonic antigen directed multiple surgical procedures for recurrent colon cancer confined to the liver.

During the past 14 years, eight patients have undergone two or more major hepatic procedures in an attempt to control metastatic colon cancer confined to the liver. A total of 19 operations was performed. In all cases, a rising level of carcinoembryonic antigen was the main indicator for surgical intervention. There were no operative deaths. Major complications occurred in 15 per cent. Following the first hepatic intervention, two patients remain alive and free of disease at 43 and 47 months (56 and 100 months since diagnosis), respectively. In the six patients who have died, survival from the first hepatic intervention ranged from 17 to 38 months (median 27 months). Age, sex, location of primary, size of primary, interval from primary operation to second operation, and site of hepatic metastasis did not influence survival. In carefully selected patients with metastatic colon carcinoma confined to the liver, encouraging results can be obtained by performing multiple surgical procedures.

Adenocarcinoma↗

Chemotherapeutic evaluation of glucarate and N-(4-hydroxyphenyl)retinamide alone and in combination in the rat mammary tumor model.

We evaluated calcium glucarate (CGT) and N-(4-hydroxyphenyl)retinamide (HPR) for their effectiveness as anti-tumor agents. For this evaluation, we tested the effects of CGT and HPR given alone or combined in the diet on the growth of established 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. When given alone, optimal doses of CGT (128.0 mmol/kg in the diet) or HPR (2.0 mmol/kg in the diet) administered daily for 25 days reduced mammary tumor sizes by approximately 15% or 20%, respectively. Suboptimal doses of CGT (64.0 mmol/kg) or HPR (0.75 mmol/kg) administered daily for 25 days only slightly inhibited tumor growth; over the 25-day period, the tumor sizes in rats on the CGT diet and in rats on the HPR diet increased by 55% and 70%, respectively, compared with a 98% increase in tumor sizes in the rats on the control diet. In contrast, the combination of suboptimal doses of CGT (64.0 mmol/kg) and HPR (0.75 mmol/kg) administered daily for 25 days decreased tumor sizes by 33%. These results are statistically significant. They show that CGT and HPR act synergistically. Consequently, lower concentrations of these agents can be used to inhibit mammary tumor development and growth.

9,10-Dimethyl-1,2-benzanthracene↗

Synergistic interaction between 13-cis-retinoic acid and glucarate: activity against rat mammary tumor induction and MCF-7 cells.

At high dietary levels in vivo, both 13-cis-retinoic acid and calcium glucarate inhibit the induction of rat mammary tumors by 7,12-dimethylbenz(a)anthracene. The present study shows that sub-optimal dietary levels of each, which individually have no effect on tumor induction, when combined together in the diet, significantly increases tumor latency and suppresses tumor frequency in the rat system. Weight gain of animals was similar in control and experimental groups. Furthermore, ineffective sub-optimal dosages of glucarate and 13-cis-retinoic acid interacted synergistically to inhibit the growth in vitro of the MCF-7 human breast cancer cells. By varying the concentrations of glucarate and 13-cis-retinoic acid independently, evidence was obtained that in combination glucarate may play an adjuvant role, with the retinoid as the effector. Thus, the results of this experimental animal study demonstrate for the first time the potential use in synergistic combination of 2 normal metabolites in non-toxic chemoprevention and chemotherapy.

Animals↗

Results of surgical excision of one to 13 hepatic metastases in 98 consecutive patients.

Metastatic carcinoma to the liver is generally considered to be associated with a poor prognosis, with five-year survival of only 20% to 30% after resection of solitary lesions. Ninety-eight consecutive patients underwent the surgical removal of one to 13 metastatic lesions from the liver. A rising carcinoembryonic antigen level was considered an indication for reexploration. All gross tumor was removed in every patient; 66 had more than one metastasis. Survival was unexpectedly high: 91 of 98 were alive at 12 months, 50 (70%) of 71 at 13 to 24 months, 23 (66%) of 36 at 25 to 36 months, 14 (74%) of 19 at 37 to 48 months, six (60%) of ten at 49 to 60 months, four (80%) of five at 61 to 72 months, and two (50%) of four 73 to 84 months after resection of multiple liver metastases. The procedure appears to be a safe and, in some patients, beneficial surgical technique for the removal of multiple hepatic metastases.

Humans↗

Heterotopic ossification within the small-bowel mesentery.

Heterotopic bone formation has been previously noted in abdominal laparotomy scars, but the presence of ectopic bone within the peritoneum is extremely rare. Our patient had recurrent formation of heterotopic bone involving the abdominal wall, peritoneum, and small-bowel mesentery. The features of various types of ectopic calcification are discussed, and several theories concerning the pathogenesis and treatment of heterotopic ossification are examined.

Abdominal Muscles↗

The use of a hand-held gamma detector improves the safety of isolated limb perfusion.

We used two hand-held gamma-detecting probes (GDP) (Neoprobe 1000 system) capable of detecting small gamma emissions to monitor leakage in patients undergoing hyperthermic isolated limb perfusion (HILP) who received 800 microCi Technetium 99m pentetate through the perfusate. The percentage of gamma-ray leakage was calculated by a simultaneous reading of two probes at 1-minute intervals (one over the precordial area and one over the thigh) and this was compared to results of simultaneous blood sampling from the perfusate and systemic circulation at 15-minute intervals for gamma well counting (GWC). The percentage of leakage recorded by the GDPs was essentially identical to that detected by the GWC (7.3% and 8.2%, respectively at the conclusion of the perfusion). The GDP gives an immediate and accurate indication of the percentage of leakage during HILP, making it a safer procedure.

Aged↗

Present status of serum markers.

Tumor markers presently in use generally meet only one or two of the criteria for the ideal marker, which are: tumor specificity, correlation with tumor bulk and stage of the disease, decrease to normal after successful treatment, and rise prior to clinical manifestations of recurrence. In addition, virtually all are elevated in some benign conditions. Currently their greatest usefulness is for confirmation of clinical suspicion and for monitoring known disease. Some tumor markers which are not effective as screening tests can be used to evaluate the patient's response to therapy. The discovery of oncogenes holds great promise for a new generation of tumor markers. Major breakthroughs in the fields of molecular biology and tumor immunology seem imminent with eventual application possibly in the treatment of cancer.

Antigens↗