PubMed Health⌕ Search

Biomedical subjects

M F Brennan

Publications and source records attributed to M F Brennan.

At least 19 recordsLinked to original sources
PubMed1992

Expression of disialogangliosides GD2 and GD3 on human soft tissue sarcomas.

METHODS: Fifty-six freshly frozen human sarcomas were studied for expression of disialogangliosides by avidin-biotin immunohistochemical staining with purified monoclonal antibodies (MoAb) 3F8 (antidisialoganglioside GD2) and R24 (antidisialoganglioside GD3). RESULTS: Ninety-three percent of the tumors tested by the immunohistochemical staining expressed GD2 and 88% expressed GD3. The intensity of expression varied among sarcomas of different histologic types. Liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma reacted strongly with 3F8 and R24. Embryonal rhabdomyosarcoma and synovial sarcoma demonstrated substantially weaker staining by either MoAb. Weakly reactive or nonreactive tumors were, in general, high-grade or metastatic sarcomas. Ganglioside extraction and thin-layer chromatography/immunothin-layer chromatography of two liposarcomas confirmed the identities of these gangliosides. CONCLUSIONS: GD2 and GD3 may indicate sites for MoAb-targeted imaging and therapy for sarcomas. The association of a diminished stainability by 3F8 and R24 with aggressive sarcomas may indicate prognostic significance.

Gangliosides↗
PubMed1992

Tendosynovial sarcoma. Clinicopathologic features, treatment, and prognosis.

BACKGROUND: Clinicopathologic features, treatment, and results are reported for 95 tendosynovial sarcomas identified from a prospective sarcoma data base established at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1982. METHODS: Eighty-five patients had definitive treatment of the primary tumor at MSKCC: Epithelial sarcomas were excluded. RESULTS: The local recurrence rate was 18%. Survival rates were not influenced by either the method of local treatment or the use of chemotherapy. The overall actuarial survival rate was 59% at 5 years (median, 92 months). For 25 patients who had resection of pulmonary metastases, the 5-year actuarial survival rate was 43% (median, 22 months) from the time of first thoracotomy. Sex, age, tumor site, and histologic subtype (monophasic versus biphasic) were not significant predictors of survival rates. Regional lymph node metastasis occurred in 3%. The incidence of distant metastasis was 49%, with an associated 5-year survival rate of 31% (median, 33 months). Tumor size was a highly significant prognostic feature, with 5-year survival rates of 86% for patients with tumors smaller than 5 cm and 22% for those with tumors larger than 10 cm (P less than 0.00001). CONCLUSIONS: Improvement of treatment results for tendosynovial sarcoma will require effective new systemic adjuvant therapeutic strategies.

Actuarial Analysis↗
PubMed1992

Effect of systemic hyperinsulinemia in cancer patients.

Data defining the isolated effect of insulin on whole body protein and glucose metabolism in cancer patients are limited. Ten normal volunteers (controls), age 55 +/- 3 years (mean +/- SEM); 8 cancer patients, age 61 +/- 3 years, weight loss 2 +/- 1% (CANWL); and 8 cancer patients, age 55 +/- 2 years, weight loss 18 +/- 2% (CAWL), were studied in the post-absorptive state. Whole body leucine kinetics were determined during a baseline and then a study period during which insulin was infused at 1.0 milliunits/kg/min to achieve a high physiological level of 71 +/- 6, 83 +/- 5, and 64 +/- 5 microunits/ml in controls, CANWL, and CAWL, respectively. Whole body net balance equals protein synthesis minus protein breakdown. Glucose disposal (mg/kg/min) is the rate of D30 infusion at steady state. Glucose disposal of CANWL and CAWL during the study period was significantly (P less than 0.05, analysis of variance) less than controls (3.91 +/- 0.6 in CANWL, 3.66 +/- 1.0 in CAWL, and 5.87 +/- 0.6 mg/kg/min in controls), suggesting resistance to insulin with respect to carbohydrate metabolism. Hyperinsulinemia, under euglycemic and near basal amino acid conditions, significantly reversed the negative postabsorptive leucine net balance (P less than 0.05, analysis of variance) by decreasing protein breakdown in controls as well as weight-stable and weight-losing cancer patients, suggesting that cancer patients are not resistant to the anti-catabolic effect of insulin with respect to whole body protein metabolism.

Body Weight↗
PubMed1992

Mechanisms of natural resistance to antifolates in human soft tissue sarcomas.

Efforts to use fresh human sarcoma cells for evaluating antifolate resistance with an in situ thymidylate synthesis assay using 5-[3H] deoxyuridine were unsuccessful because of low thymidylate synthesis activity in enzymatically disaggregated tumors. By incubating tumor cell suspensions in supplemented RPMI-1640 medium with 10% fetal bovine serum for 3 days, activity of the in situ thymidylate synthesis assay markedly increased (1.42 versus 0.03 pmol/h/10(7) cells), thus allowing 75% of samples to be evaluated for antifolate sensitivity. By criteria developed with a methotrexate-resistant and -sensitive cell line, this assay indicated that most sarcomas are naturally resistant to methotrexate (12 of 15). Natural resistance to 10-ethyl-10-deazaaminopterin and trimetrexate was also observed in 60% of the samples (nine of 15, respectively). The results from the 3-day in situ assay were confirmed by specific tests for resistance mechanisms in most sarcoma samples. The resistance mechanisms detected were impaired polyglutamylation, an increased level of dihydrofolate reductase, and amplification of this gene. These results encourage further exploration of this assay to predict response to antifolates in individual patients and to evaluate efficacy of new antifolates as candidates for clinical trial.

Aminopterin↗
PubMed1992

Management of small soft-tissue sarcoma of the extremity in adults.

To determine the significance of small (< or = 5 cm in diameter) soft-tissue sarcoma of the extremity, 174 adult patients were identified from information that had been entered prospectively into a database of 1742 patients between July 1982 and December 1990. Median follow-up was 48 months. The majority of tumors were high grade (n = 114; 66%). Local recurrence (n = 17) was seen in patients with both high-grade (11%) and low-grade tumors (7%). Distant metastases were seen in 7% of high-grade tumors and in no low-grade tumors. The overall 5-year survival rate was 94% for all patients. Grade, depth, location, type of operation, and sex did not affect 5-year survival or local recurrence-free survival. Neither postoperative adjuvant chemotherapy nor radiation therapy resulted in superior 5-year survival or local recurrence-free survival when compared with no postoperative treatment. The prognosis of these lesions is favorable, and no additional prognostic factors were identified. Inclusion of these patients into adjuvant therapy trials examining survival is inappropriate.

Adolescent↗
PubMed1992

Radiation-associated sarcoma of bone and soft tissue.

Radiation-associated sarcomas are uncommon, constituting less than 5% of all sarcomas, and generally associated with a poor prognosis. We reviewed the medical records of 565 patients with sarcoma and a second malignancy seen at our institution between 1943 and 1989; 160 of these patients (28%) were considered to have a radiation-associated sarcoma. The most common diagnosis for which radiation had been given was breast cancer (26%), followed by lymphoma (25%) and carcinoma of the cervix (14%). The most common histologic types of radiation-associated sarcoma were osteogenic (21%), malignant fibrous histiocytoma (16%), and angiosarcoma/lymphangiosarcoma (15%). Most of the tumors were high grade (87%). Three variables had prognostic significance in multivariate analysis: the presence of metastatic disease, the completeness of operative resection in patients with localized disease, and the size of the primary tumor in patients who underwent complete resection of the sarcoma. Survival was independent of histologic subtype or site of disease.

Adolescent↗
PubMed1992

Acute pancreatitis from intussusception of a gastric polyp in a patient with Gardner's syndrome.

Gastric polyps in Gardner's syndrome are usually benign small fundic gland neoplasms with little clinical significance. We report a case of gastroduodenal intussusception secondary to a large benign gastric polyp in a 44-year-old woman with Gardner's syndrome who presented with acute pancreatitis. The intussuscepted polyp caused obstruction of the ampulla of Vater with subsequent acute pancreatitis.

Acute Disease↗
PubMed1992

The effect of insulin on glucose and protein metabolism in the forearm of cancer patients.

This study was designed to study the effect of systemic hyperinsulinaemia (INS) on glucose and protein metabolism in cancer patients. Sixteen cancer patients (8 > 10% weight loss (WL); 8 < 10% weight loss (NWL)) were compared with 12 healthy controls. Glucose uptake (GU) and phenylalanine (PHE) exchange kinetics were measured across the forearm in the postabsorptive state (PA) and in response to INS (71 +/- 5 microU ml-1). At steady state in response to INS, the negative PA PHE net balance became significantly positive, and GU significantly increased, for cancer and control groups, with no significant differences between the two groups. Subset analysis of NWL cancer vs. WL cancer found no difference between WL and NWL for the change in PHE balance from PA and INS, however GU increased significantly only for the NWL group between PA and INS. These data indicate that cancer patients are not resistant to the anabolic effect of INS on protein metabolism, regardless of weight loss, but are resistant to the effect of INS on glucose metabolism when further along in the disease process as evident by more significant weight loss. This differential response to the effect of INS can be exploited in an attempt to promote protein accrual in weight-losing cancer patients.

Aged↗
PubMed1992

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.

Actuarial Analysis↗
PubMed1992

Surgical treatment of gastric cancer. Proximal, mid, and distal stomach.

At present, only radical surgical resection of gastric cancer offers a chance for cure. The objective of an operation for patients with disease that is confined locally is to maximize the potential for cure. The objective for patients with advanced incurable disease, obstruction, hemorrhage, and intractable pain is to provide the best palliation. The evaluation, staging, and surgical management of gastric cancer are described.

Humans↗
PubMed1992

Follow-up.

Explore the source record for details and available documents.

Flushing↗
PubMed1992

Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.

Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.

Adenoma↗
PubMed1992

Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity.

The use of amputation in extremity soft tissue sarcoma has been decreasing at Memorial Sloan-Kettering Cancer Center (MSKCC) over the last 15 years. In an attempt to define the efficacy and future role of amputation in extremity soft tissue sarcoma, a prospective sarcoma database compiled at MSKCC from July 1982 to January 1990, consisting of 649 patients, was analyzed in a retrospective fashion. Ninety-two patients underwent amputation, and 557 had a limb-sparing procedure. Patients selected for amputation were those who had large (T greater than or equal to 5 cm) high-grade tumors that invaded major vascular or nervous structures. The amputation group achieved significantly better local control than the limb-sparing group (p = 0.007). No survival benefit could be demonstrated, however, in the groups selected for amputation (i.e., large, high-grade tumors) when compared with patients undergoing a limb-sparing procedure with similar tumors. Prevention of local recurrence by amputation also did not improve survival in this group compared with similar patients undergoing limb-sparing surgery who did develop a local recurrence. The group of patients with high-grade tumors 10 cm or larger who received chemotherapy did have a significant improvement in survival (p = 0.01) compared with a similar group of patients who did not receive chemotherapy, regardless of the type of operation. The prognosis of patients most likely to undergo an amputation for extremity soft tissue sarcoma (those with high-grade, large tumors) is not related to their local disease, but rather to the risk of distant metastases. Therefore, amputation in this cohort of patients can be recommended only when a limb-sparing procedure cannot achieve gross resection of tumor while still preserving a useful extremity, because amputation improves only local control and does not address distant disease. Further improvement in survival in this group of patients will be dependent on better systemic treatment for extremity soft tissue sarcoma, and not on more radical surgery.

Adolescent↗
PubMed1992

Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients.

The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient.

Amino Acids↗
PubMed1992

Effect of hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans.

Data documenting the isolated effect of systemic hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans are limited. Using steady-state [14C]leucine kinetics, 10 normal volunteers were studied in the baseline postabsorptive state and then under euglycemic, hyperinsulinemic (71 +/- 5 microU/ml), and euleucinemic conditions. Systemic hyperinsulinemia resulted in a significant decrease in whole body and forearm leucine rate of appearance (Ra) by 17 and 37%, respectively, (P less than 0.0003, 0.03), without a significant change in the nonoxidized rate of disappearance for either (P = 0.23, 0.66). The baseline contribution of total body skeletal muscle (TBSM) leucine Ra and rate of disappearance (Rd) to whole body leucine Ra and Rd was 27 +/- 6 and 24 +/- 5%, respectively. During hyperinsulinemia TBSM Ra decreased by 34%, whereas whole body Ra decreased by 16%. We conclude that the primary effect of insulin in the whole body and skeletal muscle is to decrease leucine release from protein without a significant effect on leucine incorporation into protein. This antiproteolytic effect of insulin is more pronounced in skeletal muscle than in other tissues in the body.

Amino Acids↗
PubMed1992

Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.

PURPOSE: The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS: Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS: Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS: The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.

Adult↗
PubMed1992

The changing role of amputation for soft tissue sarcoma of the extremity in adults.

The role of amputation in soft tissue sarcoma of the extremity has decreased at Memorial Sloan-Kettering Cancer Center during the last 20 years. In an attempt to determine the reasons for this change in therapy, an analysis of two separate databases involving 1,057 patients compiled during the periods of 1968 to 1978 and 1982 to 1990 was performed. The patients requiring amputation for soft tissue sarcoma of the extremity in the two databases (n = 233) were compared in an attempt to determine any significant differences between the two time periods. The groups were specifically compared for differences in risk factors, indications for amputations and the effect a decreasing incidence of amputation in the 1982 to 1990 group had on local recurrence and overall survival between the two groups. Despite similarity of risk factors and indications for amputation, the decreased incidence of amputation during the 1982 to 1990 period was associated with a significant decrease in local recurrence after amputation and no significant change in overall survival compared with the 1968 to 1978 group. Absence of local recurrence was associated with significant improvement in survival. Possible reasons for the shift in therapy, as well as the present and future role of amputation in soft tissue sarcoma of the extremity, are discussed.

Adolescent↗