The implications of angiogenesis for the biology and therapy of cancer metastasis.
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Angiostatins↗
Biomedical subjects
L M Ellis
Publications and source records attributed to L M Ellis.
Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas.
BACKGROUND: Limb-sparing surgery for soft tissue sarcomas of the extremities may result in microscopically positive surgical margins. The consequences of these microscopically positive margins are unknown. We have analyzed the influence of surgical margins on local disease control and overall survival in patients with extremity soft tissue sarcomas who received preoperative radiation therapy followed by limb-sparing surgery. METHODS: Ninety-five consecutive patients with intermediate and high grade extremity sarcomas who received preoperative radiation therapy and limb-sparing surgery were identified from a soft tissue sarcoma data-base. The clinical outcome of 24 patients who had microscopically positive surgical margins was compared with that of 71 patients who had clear surgical margins. RESULTS: Multivariate statistical analysis revealed that patients with microscopically positive surgical margins or intraoperative tumor violation had an increased risk for local failure. High grade, large size, and intraoperative violation of the tumors were associated with decreased overall survival. However, neither the presence of a positive surgical margin nor the occurrence of a local failure adversely affected overall survival. CONCLUSIONS: Achieving negative surgical margins in patients with intermediate and high grade extremity sarcomas enhances local disease control but does not measurably improve overall survival. These data should be factored into patient management decisions in cases where the goal of achieving clear surgical margins requires amputation or the significant functional compromise of the extremity.
Actuarial Analysis↗
Surgical management of hepatoma.
For the majority patients with HCC, the prognosis is poor. Only a fraction of patients will be resectable at the time of their diagnosis. For the oncologic surgeon caring for such patients, the challenges are multifaceted. First, he or she must have a familiarity with current imaging techniques and reliable support from a radiologist to determine whether a given patient can be technically resectable. We rely most heavily upon the initial diagnostic CT scan followed by the staging CTAP in order to define the resectable patient as clearly as possible. Additionally, the risk of postoperative hepatic failure must be assessed. Careful physical exam, blood chemistries, and volumetric analysis of CT scans demand much judgment on the part of the surgeon. While some patients are clearly capable of undergoing a resection, and others are clearly inoperable due to poor hepatic function, a large group of patients exist in a "gray area" where resection can be entertained but the risk of hepatic failure looms large. In this group the use of the ICG retention test or the 14C-aminopyrine breath test are occasionally useful. Further research into better assessment of hepatic reserve is clearly needed. Once a laparotomy is undertaken, IOUS is a key component of intraoperative staging and the final determinant of resectability. Resection itself must be performed with three goals: Resection of all disease with negative surgical margins, retention of as much hepatic parenchyma as possible in keeping with oncologic principles, and maintenance of hemodynamic stability with minimal transfusion requirements in an effort to minimize the stress of surgery. The combination of vascular control and the porta hepatis (and IVC where necessary), segmental hepatic resection where appropriate, and ultrasonic dissection can accomplish these goals. Intrahepatic recurrence, despite adequate resection, can be expected in many patients, and few will be candidates for a second resection. For this reason, and because most patients are unresectable at presentation, the oncologic surgeon must be familiar with palliative options available for his patients, as well as the surgical management of operable tumors. Close collaboration with one's colleagues in medical oncology, invasive radiology, and gastroenterology are critical to the optimal care of this difficult patient population.
Carcinoma, Hepatocellular↗
Expression of CD44R1 adhesion molecule in colon carcinomas and metastases.
CD44 is a cell surface adhesion molecule postulated to control lymphocyte recirculation by facilitating entry into lymphoid tissue. Tumour cells transfected to overexpress the epithelial variant CD44R1 readily gain access to lymph nodes and distant metastatic sites in animal models, possibly by mimicking circulating lymphocytes. To investigate if human tumours display altered CD44 expression we performed reverse transcriptase a polymerase chain reaction (PCR) analysis of CD44 in 49 specimens from normal colonic mucosa, primary colon and rectal tumours, normal liver, and metastases of 20 patients. The haematopoietic variant CD44H was the principal isoform amplified in all of the specimens, However, 12/14 primary tumours and 16/16 metastatic potential. Moreover, the relative increase with only 2 of 13 normal mucosa specimens. This increase in CD44R1 relative to CD44H expressed by human colon carcinoma cells may increase their metastatic potential. Moreover, the relative increase in PCR amplification of CD44R1 compared with that of CD44H may provide a sensitive method for detecting primary and metastatic colon carcinoma cells in small biopsy specimens.
Base Sequence↗
A rapid colorimetric in situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas.
We have developed a rapid colorimetric in situ mRNA hybridization procedure to analyze epidermal growth factor receptor (EGF-R) transcripts in paraffin-embedded surgical specimens of human colon carcinomas. This technique is based on the use of 24-base oligonucleotide probes labeled with 6 biotin molecules at the 3' end. mRNA integrity was verified using a hyperbiotinylated 30-residue-long deoxythymidylate oligonucleotide probe, and the specificity of the reaction was confirmed by using labeled EGF-R-specific sense and antisense probes. Avidin alkaline phosphatase detection and the capillary technology used in the Microprobe System allowed for completion of the procedure in under 5 h. The human A431 epidermoid carcinoma cells growing in culture and fixed with formalin as well as paraffin-embedded sections of this tumor growing s.c. in nude mice served as positive controls. In situ hybridization with antisense EGF-R oligonucleotide probes directly correlated with EGF-R mRNA and protein levels observed by Northern blot and immunohistochemistry, respectively. In situ hybridization of paraffin-embedded sections of primary human colon carcinoma and metastases from liver and lymph node revealed cell-specific staining with EGF-R antisense oligonucleotide probes that correlated directly with Northern blot and immunohistochemistry analyses. Since this rapid and sensitive in situ mRNA hybridization technique can be used in properly preserved paraffin-embedded tissue, it allows for retrospective analyses of human tumor specimens using archival material.
Animals↗
Stereological study of mouse uterine and in vitro grown blastocysts: cell numbers and volumes.
Mouse blastocysts were studied to determine if there were differences in cell number and volumes between those that were 1) derived from the uterus prior to implantation on the afternoon of day 4 of pregnancy and 2) those that were cultured for 72 hr from two-cell-stage embryos. Blastocysts were fixed, embedded in resin, and serially sectioned at 1.5 or 2 microns. Photographic prints of alternate sections were used to count the numbers of inner cell mass (ICM) and trophectoderm cells. Cavalieri's direct estimator was applied to the same prints to estimate the volume of the whole blastocyst. Point counting was used to determine the volumes of the ICM, trophectoderm, and zona pellucida. The number of cells and size of the ICM were similar between the two groups of blastocysts, although it was found that the ICM of uterine embryos that did not have a zona pellucida were smaller than the ICM of those that did. There were twice as many trophectoderm cells in the blastocysts that were cultured from two-cell embryos, and these cells were also found to be larger. Furthermore, the volume of the zona pellucida was less in the uterine blastocysts. This study indicates that, while trophectoderm proliferation is enhanced in vitro, the ICM is more constant and thus may be self-regulating and independent of the growth conditions of the blastocysts as a whole. This study also suggests partial zona lysis occurs in utero and occurs either at a reduced rate or not at all in vitro.
Animals↗
Laparoscopic feeding jejunostomy tube in oncology patients.
Laparoscopic-guided feeding jejunostomy tubes are being utilized in two specific groups of patients: (i) patients with resectable or locally advanced adenocarcinoma of the pancreas treated on a protocol of preoperative chemoradiation, who may require nutritional support, and (ii) patients with metastatic or obstructing foregut tumours who require a route for delivery of fluid and medication. The technique, rationale and results for our first 17 patients who underwent laparoscopic placement of a tube jejunostomy are described. Laparoscopic feeding tube placement is a safe and cost-effective method to gain enteral access and stage the oncology patient's disease. This procedure is less invasive than standard surgery for tumour staging and feeding tube placement, and facilitates formula advancement and the patient's early hospital release without morbidity or mortality.
Aged↗
Current strategies for the treatment of hepatocellular carcinoma.
Although hepatic resection for hepatocellular carcinoma is the only known modality that offers an opportunity for cure, the practicing oncologist must be aware of alternative modes of therapy. A multidisciplinary approach between surgeon, medical oncologist, and invasive radiologist is necessary in exploring all potential therapeutic options. The oncologist must not only consider the stage of the tumor, but must also take into account the functional reserve of the nontumor-bearing liver in selecting appropriate therapy. More recently, hepatic transplantation has been recognized as a potential curative modality for specific tumor types and stages. Percutaneous ethanol injection and chemoembolization are excellent palliative measures. However, it remains clear that new and innovative techniques are necessary in the therapeutic, adjuvant, and palliative settings in the comprehensive care of the patient with hepatocellular carcinoma.
Aneuploidy↗
Perioperative nutritional support.
In selected malnourished patients, perioperative nutritional support can decrease the morbidity and mortality rates associated with major surgical procedures. Preoperative nutritional support should be delivered via the gastrointestinal tract whenever feasible, generally in the form of enteral diets, which can be given via a feeding tube or as a dietary supplement. Patients with a functional gut who cannot eat because of anorexia or upper gastrointestinal tract obstruction are candidates for preoperative tube feedings. Total parenteral nutrition should be the mainstay of nutritional support when the gastrointestinal tract cannot be used adequately. An improvement in nutritional indices (e.g., serum transferrin, lymphocyte count) may be associated with decreased perioperative morbidity, although the strength of this relation is not clear. In the absence of improvement in such indices, the duration of nutritional support required to decrease operative morbidity is unknown. Postoperatively, enteral tube feedings (delivered via a nasojejunal tube or feeding jejunostomy) should be provided to all preoperatively malnourished patients with a functional gastrointestinal tract who are unable to consume adequate calories orally. Postoperative TPN should be reserved for malnourished patients with a nonfunctional gut or for patients who develop a postoperative complication that precludes enteral feeding. Current nutritional formulas have often neglected the metabolic and nutritional requirements of the intestinal tract. In the future, the combined use of specific nutrients and growth factors may improve nutritional rehabilitation in catabolic patients.
Enteral Nutrition↗
Differential role of prostaglandin E1 on tumor metastasis.
Previous studies from our laboratory have shown that intravenous (iv) infusion of pharmacologic doses of prostaglandin E1 (PGE1) inhibits "spontaneous" metastases in mice bearing Lewis Lung carcinoma (LLC). This study was done to determine the effect of iv PGE1 on "artificial" metastases. Male hybrid mice (20 g) underwent iv catheterization and were begun on continuous infusions of either PGE1 at 10 micrograms/kg/min or 0.9% NaCl (NS). After 2 days, each mouse received an iv injection of 10(5) viable LLC cells and was continued on the infusion regimens. Pulmonary metastatic nodules were enumerated and measured 12 days after injection. The iv infusion of PGE1 increased the metastatic rate 6-fold, the number of metastases greater than or equal to 2 mm in diameter 7-fold, and the number of metastases greater than or equal to 3 mm in diameter 14-fold. Thus, PGE1 demonstrates differential effects on tumor metastases, acting as a promotor of artificial metastases, in contrast to its antimetastatic effect on an intact primary tumor. When the promotional effect of iv PGE1 on artificial metastases is evaluated in light of our previous studies, it can be concluded that the inhibitory effect of PGE1 on spontaneous metastases from an intact tumor is secondary to the effect of PGE1 at the level of the primary tumor, and not in the circulation or at the target organ of metastases (lung).
Alprostadil↗
Techniques for obtaining the diagnosis of malignant breast lesions.
Although fine needle aspiration is an efficacious method for diagnosing the palpable breast cancer, a negative aspirate does not exclude the presence of a malignancy. Open breast biopsy remains the standard of care in diagnosing a malignant breast lesion. All breast biopsies should be planned as if the scar were to be excised by a definitive surgical procedure (either mastectomy or tylectomy). New lesions in the treated breast require immediate biopsy because of the high likelihood of recurrent disease. Preferably, definitive surgery for malignancy should not be delayed more than 2 weeks after biopsy.
Biopsy↗
Inhibition of tumor growth and metastasis by chronic intravenous infusion of prostaglandin E1.
The role of prostaglandins and their synthesis inhibitors in malignant disease is undefined. The following studies were done to determine the effects of continuous intravenous prostaglandin E1 (PGE1) or a prostaglandin synthesis inhibitor, indomethacin, on tumor growth and metastasis in mice bearing Lewis lung carcinoma. Male B6D2F1 mice underwent tumor implantation in the right axilla on day 0. After 10 days of tumor growth, mice underwent intravenous (IV) catheterization and were infused with either PGE1 at 3 micrograms/kg/minute (PG-LOW), PGE1 at 6 micrograms/kg/minute (PG-HIGH), indomethacin (INDO) at 1 microgram/kg/minute, or normal saline (NS). After 10 days of infusion, tumor volume, tumor weight, and the number of metastases greater than 2 mm in diameter were significantly decreased, and tumor doubling time was significantly prolonged in the PG-HIGH group compared to NS controls. None of the other experimental groups showed differences in these parameters. A second experiment with a similar experimental design was done infusing PGE1 at 6 micrograms/kg/minute and at 12 micrograms/kg/minute to determine the maximum dose response of IV PGE1. Again a decrease in tumor volume, tumor weight, and metastatic rates were identified when compared to saline control, but there were no significant difference between the two doses of PGE1.
Alprostadil↗
Lability of steroid hormone receptors following devascularization of breast tumors.
Ischemia may invalidate hormone-receptor analyses. This study determined the effects of progressive ischemia on steroid hormone-receptor analyses. Breast cancer was induced in 50- to 60-day-old female Holtzman rats by intragastric administration of 25 mg of 7,12-dimethylbenz[a]anthracene. After 90 days, rats were anesthetized and breast tumors were devascularized in vivo. At 0, 30, 60, 90 and 150 minutes, a biopsy specimen from each tumor was taken and rapidly frozen. Steroid binding capacity for estrogen (ER), progesterone (PR), and androgen (AR) receptors was determined by incubation with tracer receptor ligand. Ischemia decreased ER and AR levels by 30 minutes, whereas PR levels were unchanged through 150 minutes of ischemia. Following mastectomy, tylectomy, or breast biopsy, PR may be the most reliable of the hormone receptors for determining endocrine-responsive breast cancer. However, for accurate determination of all hormone receptors, specimens should be frozen in liquid nitrogen immediately, then preserved at -70 degrees C, or processed immediately.
9,10-Dimethyl-1,2-benzanthracene↗
Correlation of estrogen, progesterone, and androgen receptors in breast cancer.
Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.
9,10-Dimethyl-1,2-benzanthracene↗
Central venous catheter vascular erosions. Diagnosis and clinical course.
Central venous catheter (CVC) vascular erosions are difficult to diagnose, and they cause serious complications. From 1985 to 1987, ten patients receiving the surgical services at the University of Florida suffered CVC vascular erosions. By chest roentgenogram, nine CVC tips were in the superior vena cava (SVC), although three catheter tips abutted the lateral wall of the SVC. One catheter tip was in the right atrium. All patients had sudden onset of symptoms, the most common of which was shortness of breath. Initial diagnosis was respiratory insufficiency in five patients, cardiac failure in three patients, pulmonary embolism in one, and sepsis in one. Four patients required intensive care. Two patients suffered pericardial tamponade, and pleural effusions developed in eight patients. One patient died of cardiac arrest. The average time interval from CVC placement to onset of symptoms was 60.2 hours, and from the onset of symptoms to the time of diagnosis, the interval was 16.7 hours. The mean volume obtained at thoracentesis was 1324 ml and at pericardiocentesis was 250 ml.
Adult↗
Inflammatory breast cancer: advances in therapy.
Inflammatory breast cancer is the most aggressive breast neoplasm and one of the most ominous solid tumors. Because of distinct clinical characteristics, diagnosis can usually be made on clinical grounds. Biopsy including the overlying skin may demonstrate dermal lymphatic invasion, although the absence of dermal lymphatic invasions should not deter aggressive therapy. Surgery or irradiation alone has little effect on the natural history of this disease since lymphatic invasion and distant metastases are often present at presentation. Inflammatory breast cancer should be considered a systemic disease. Accordingly, aggressive combined modality therapy including multi-drug chemotherapy, surgery, and irradiation have prolonged disease-free survival and overall survival.
Antineoplastic Combined Chemotherapy Protocols↗
Partial hepatectomy decreases pancreatic parenchymal enzyme activity.
In previous studies of liver regeneration following partial hepatectomy (PH) in rats, we noted a decrease in serum amylase activity. The present study was carried out to determine if the decrease in serum amylase following PH corresponds to a decrease in pancreatic parenchymal exocrine enzyme activity. Male Wistar rats (275 g) underwent either 60% PH or sham laparotomy (SL). A third group, serving as controls (CON), received no surgical procedure. All groups were pair-fed a nutritionally balanced diet. After 48 hr, pancreas, blood, and liver were removed for analysis. Results showed that PH decreased pancreatic parenchymal protein by 43%, lipase by 44%, and trypsin by 22% compared to controls. Serum amylase decreased by 28%, a finding similar to previous experiments. However, pancreatic parenchymal amylase activity was not affected. It remains to be determined whether the reduced pancreatic function affects digestion and absorption.
Amylases↗
The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome.
The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.
Abortion, Spontaneous↗