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Biomedical subjects

J D Beatty

Publications and source records attributed to J D Beatty.

At least 73 records · Page 4Linked to original sources
PubMed1988

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

Aged↗
PubMed1988

The inferior trapezius musculocutaneous flap in head and neck reconstruction.

The trapezius musculocutaneous flap based on the descending branch of the transverse cervical vessels has been used to reconstruct a variety of large and complex defects in the head and neck region. Forty-three flaps were performed in 41 patients over a period of 26 months. Excellent reconstruction was achieved in 37 patients. Six total and nine partial flap failures were noted. There were 8 deaths during this time, 2 attributable directly to flap failure. Patient positioning during surgery and the tedious dissection are disadvantageous. The advantages of this flap are its thinness, long reach, and a posterior donor defect. These attributes are ideally suited for certain complex reconstructive endeavors in the head and neck.

Adolescent↗
PubMed1988

Tumor uptake as a function of tumor mass: a mathematic model.

Inverse correlations of tumor uptake (u), measured in percent injected dose per gram, with tumor mass (m) are demonstrated for phospholipid vesicle, nonspecific and specific monoclonal antibody tracers. Correlation coefficients implied u = B mA in 11 different animal experiments. Experimental exponent (A) values lay in the range -0.28-0.64 with a mean of -0.43 while intercept (B) values varied from 3 to 18. Spherical and cylindrical tumor models implied exponents of -0.33 and -0.5, respectively. Comparison of three implantation sites of the human LS174T xenograft revealed a narrow range of exponents (-0.38- -0.46) indicating a consistent geometry for this tumor. Blood flow to the lesion site and inside its volume (as dictated by tumor size) are factors in tumor uptake. Our results indicate that biodistribution data should include the variation of tumor uptake with mass. For less than 10 g lesions, we predict that radiation absorbed dose will be highly dependent upon tumor size.

Animals↗
PubMed1987

Method of analysis of non-competitive enzyme immunoassays for antibody quantification.

A computerized analysis of a quantitative enzyme-linked immunoadsorbent assay (EIA) using a non-specific immunoglobulin (IgG) of known concentration as the standard has been developed for measuring specific antibody levels in serum without the need for affinity purification of the positive control antibody. The computer program utilized logit-log linear regression analysis of sigmoid serial dilution curves plus a weighted least-squares best curve fit analysis and an iterative manipulation to eliminate errant data points. The EIA was performed using serial dilutions of standard and unknown antibodies, and a double sandwich technique. A comparison of antibody levels determined by EIA using non-specific IgG as a standard relative to antibody levels determined using affinity-purified specific antibody as a standard were 1.04, 0.53, 0.48, and 0.97 for four different polyclonal antibody systems. Five monoclonal antibodies to carcinoembryonic antigen gave ratios as described above of 1.07, 1.59, 1.73, 2.32, and 2.42. The corresponding antibody affinity constants (1/mol) were 1.0 X 10(8), 3.8 X 10(8), 5.5 X 10(9), 1.8 X 10(10), and 2.6 X 10(10) respectively. This method permits accurate quantification of serum antibody levels when affinity-purified antibodies are not readily available and avoids errors due to loss of antibody activity during affinity purification.

Amino Acids↗
PubMed1987

Measurement of monoclonal antibody affinity by non-competitive enzyme immunoassay.

Enzyme-linked immunoadsorbent assay (EIA) has widespread use for the measurement of antibody concentration. The affinity constant (Kaff) of the antibody has an effect upon the quantification by EIA. It is thus important to be able to measure Kaff by solid-phase EIA. Based upon the Law of Mass Action and using serial dilutions of both antigens (coating the plate) and antibody, Kaff has been measured by EIA. A microtiter plate was coated with antigen (Ag) and then incubated with monoclonal antibody (Ab). The plate was sequentially incubated with a second enzyme-antibody conjugate (EAC) and with the enzyme substrate. The amount of Ab adherent to Ag on the plate [Ag Ab] and [Ag2 Ab] was reflected by the enzyme product measured by OD. The use of serial dilutions of Ab resulted in a sigmoid curve of OD versus logarithm of total Ab added to the well. Comparison of the OD at the upper plateau (OD-100) for different antibodies was a reflection of the relative number of epitopes on the Ag that were identified by the different antibodies, provided excessive EAC was used. [Ab]t and [Ab']t were the measurable total antibody concentrations in the wells at OD-50 and OD-50' for plates coated with [Ag] and [Ag'], respectively. [Ag] and [Ag'] were not true antigen concentrations, but were a measure of antigen density on the plate. For [Ag'] = [Ag]/2, Kaff = 1/2(2[Ab']t-[Ab]t. Using five different anti-CEA antibodies and different proportions of CEA in the coating solution, Kaff was measured. Kaff determined by EIA correlated well with Kaff measured by soluble phase inhibition assay. This EIA method of estimation of Kaff is simple, rapid, and reliable.

Antibodies, Monoclonal↗
PubMed1987

Therapy of peritoneal carcinomatosis of human colon cancer xenografts with yttrium 90-labeled anti-carcinoembryonic antigen antibody ZCE025.

The present study was undertaken to determine whether an anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAB), labeled with the potent beta emitter yttrium 90, could alter the growth of diffuse intraperitoneal carcinomatosis of colon cancer. Nude mice bearing the CEA-producing human tumor line LS174T received therapy with the anti-CEA MAB ZCE025 90Y. Animals were evaluated 12 days after therapy. Untreated animals had a mean (+/- SEM) tumor burden of 3.99 +/- 0.10 g, while animals treated with ZCE025 90Y had 0.29 +/- 0.04 g present. This decrease was significant compared with the 1.31 +/- 0.16 g of tumor present in animals treated with a 90Y-labeled nonspecific antibody 96.5c. The therapeutic effects seen with ZCE025 90Y suggest a potentially useful role for 90Y-labeled anti-CEA MABs in the treatment of gastrointestinal carcinomatosis.

Animals↗
PubMed1987

Imaging of colon carcinoma with 111-indium-labeled anti-CEA monoclonal antibodies (Indacea) prior to surgery.

Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.

Antibodies, Monoclonal↗
PubMed1987

Transhiatal esophagectomy.

Thirty-six patients underwent resection of the thoracic esophagus without a thoracotomy for the management of cancer of the cervical esophagus (2 patients), middle third and lower third of the esophagus (4 patients and 23 patients, respectively), and the gastroesophageal junction (17 patients). In addition to a total esophagectomy, two patients required a laryngectomy and seven patients had a total gastrectomy. Intraoperative bleeding occurred in three patients. Postoperative complications included subphrenic abscess (Candida) (2 patients), diaphragmatic hernia (1 patient), and salivary fistula (11 patients). Three patients died in the postoperative period from necrosis of interposed colon, pneumonia, and liver failure due to liver metastasis. The average blood loss was 1,300 ml, the duration of surgical procedure was 5.3 hours, and the hospital stay was 21 days. The survival rates at 1, 2, and 3 years were 80 percent, 50 percent, and 33 percent, respectively. Transhiatal esophagectomy can be considered a sound alternative to transthoracic esophagectomy in the management of tumors involving the cervical and lower esophagus. Small lesions of the middle third should also be considered for this procedure, however, bulky lesions of the upper esophagus are better removed by thoracotomy.

Adenocarcinoma↗
PubMed1986

Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries.

One hundred patients were entered on a randomized prospective protocol to evaluate the effectiveness of hepatic resection of single as well as multiple hepatic metastases from colorectal primaries in combination with continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) via the implantable pump (Infusaid, Intermedics Infusaid Inc., Norwood, MA). The eight patients with single metastases were randomized to hepatic resection alone (three patients) or hepatic resection plus CHAI (five patients). The 22 patients with resectable multiple metastases were randomized between receiving CHAI only (12) or CHAI after resection of all metastases (10). Patients who had positive portal lymph nodes (14) were all treated with CHAI. Patients with unresectable metastases (31) were randomized between intravenous 5-fluorouracil or CHAI of FUDR. FUDR was alternately infused every 2 weeks at a dose of 0.1 mg/kg/24 hour escalated to .3 mg/kg/24 hour with heparinized saline as the alternative infusate. The median follow-up of all patients was 20 months. All patients with multiple resectable metastases had at least a partial response (PR) to the CHAI (PR defined as greater than or equal to 50% decrease of the sum of the products of the diameters of the lesions measured on computerized axial tomography scans), and four patients given CHAI only had no metastases in the liver on relaparotomy. Patients with resection and CHAI had a better survival than patients with CHAI only; however, the difference was not significant. Patients with positive portal nodes and CHAI had a lower PR (36%) than patients with unresectable disease treated with CHAI (52%). Patients with positive portal nodes or metastatic disease outside of the liver did significantly worse than patients with unresectable disease treated with CHAI.

Clinical Trials as Topic↗
PubMed1986

The effect of tumor CEA content and tumor size on tissue uptake of indium 111-labeled anti-CEA monoclonal antibody.

This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)-labeled anti-CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT-6 was used as a control. Tumor CEA levels (ng/g of tumor +/- standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT-6, 0; WiDr, 105 +/- 5.7; LS174T, 2052 +/- 198; SW403, 17,575 +/- 1,785. The 111In-labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue +/- SEM. The non-CEA-producing tumor, EMT-6, showed the lowest tumor uptake (1.4 +/- 0.3). WiDr, an intermediate CEA-producing tumor, showed some tumor uptake (16.4 +/- 1.5). The high CEA-producing tumors, SW403 and LS174T, had high tumor uptake (29.5 +/- 5.0 and 51.1 +/- 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor-to-blood (T/B), tumor-to-liver (T/L), and liver-to-blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = -0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.

Animals↗
PubMed1986

Imaging of human colorectal adenocarcinoma with indium-labeled anticarcinoembryonic antigen monoclonal antibody.

Twenty patients with 21 primary colorectal adenocarcinomas were studied with 2 mCl (7.6 X 10(7) becquerels) of indium-labeled monoclonal antibody (200 micrograms) specific for carcinoembryonic antigen (CEA). Fifteen lesions (71%) were visualized by gamma camera scintigraphy at 48 hours postinjection. Tumors that were identified by immunoscintigraphy were large (38.10 +/- 17.76 cm3 vs 6.00 +/- 1.65 cm3), had a grossly fungating component, had a high content of CEA by enzyme immunoassay (12.9 +/- 3.6 micrograms/g vs 3.3 +/- 1.7 micrograms/g), and had an apical and/or intraluminal staining pattern on immunohistologic section. Patients whose tumors were visualized had a low serum CEA level (1.9 +/- 0.4 ng/mL vs 14.6 +/- 8.0 ng/mL). Prospective selection of patients for follow-up imaging or therapy with radiolabeled monoclonal antibodies may be feasible using these measurements.

Antibodies, Monoclonal↗
PubMed1986

Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody.

Patients with primary, recurrent, or metastatic colorectal adenocarcinoma were given injections of 200 micrograms of anticarcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111In (Indacea). Patients were imaged at 24 and 48 h. Celiotomy was performed on 40 patients between 3 and 17 days post-Indacea injection. Of 16 primary tumors, 11 (69%) were imaged. Of six extrahepatic recurrences, none was imaged. Intrahepatic metastases were visualized as negative images in 10 of 24 (42%) patients. On the basis of the activity in tissue expressed as a percentage of the total radioactive dose per kg injected into the patient (% ID/kg), extrahepatic tumors that were imaged using Indacea had a significant uptake of radiolabel in the tumor [5.99 +/- 0.91% ID/kg (SE)] and in the associated normal mesenteric lymph nodes (12.0 +/- 2.4% ID/kg). The CEA content of these tumors was high (13.3 +/- 4.7 micrograms/g), and, histologically, the CEA was located primarily apically or intraluminally. Intrahepatic tumor imaging correlated only with tumor size. The greatest Indacea uptake was seen in normal liver (22.1 +/- 3.2% ID/kg). Low Indacea uptake was seen in fat (0.21 +/- 0.05% ID/kg) and bowel wall (1.11 +/- 0.17% ID/kg). In conclusion, Indacea imaging of colorectal carcinoma is specific for high concentrations of accessible CEA in CEA-bearing tumors or in lymph nodes draining these tumors. The successful clinical use of monoclonal antibodies for tumor imaging and therapy will require careful selection of patients for a number of antigen-related parameters including antigen content and distribution in tumors. This information will only come from careful correlation between image results and tissue analysis. High uptake by normal liver tissue is the major unresolved problem with labeled antibody imaging.

Antibodies, Monoclonal↗
PubMed1986

Testis imaging with 111In-labeled anticarcinoembryonic antigen monoclonal antibody: identification of carcinoembryonic antigen in normal germ cells.

A monoclonal antibody to carcinoembryonic antigen (CEA) labeled with 111In (Indacea) was used to image tumors in patients with colorectal cancer. The anti-CEA antibody has a high affinity (2.6 X 10(10) M-1) for CEA and does not cross-react with normal cross-reacting antigen, biliary glycoprotein-1, or tumor-extracted, CEA-related antigen. During the course of these studies, it was noted that a significant number of male patients (20 of 27, 74%) showed uptake of Indacea in the testes. In order to determine if the Indacea uptake was specific, 20 testicular specimens were analyzed by immunohistological methods using five different anti-CEA CEA monoclonal antibodies recognizing five different epitopes on CEA. In 18 cases (90%) germ cells were uniformly stained by all five antibodies. Fresh frozen testis tissue was homogenized in water and precipitated with 1.0 M perchloric acid. The supernatant contained a CEA-like material as measured by an enzyme immunoassay specific for CEA. The same supernatant was radiolabeled with 125I and immunoprecipitated with anti-CEA monoclonal antibodies. Sodium dodecyl sulfate:polyacrylamide gel electrophoresis of the immunoprecipitates revealed a single species (Mr 180,000) which was indistinguishable from CEA. This study documents the first description of CEA in the germ cells of normal testis. The CEA in the testis was accessible to circulating monoclonal antibodies in the majority of male patients tested.

Adult↗
PubMed1986

Continuous hepatic artery infusion with an implantable pump: problems with hepatic artery anomalies.

The implantable pump for continuous hepatic artery chemotherapy requires even distribution of the chemotherapy to the whole liver for maximum efficacy. The hepatic arterial supply and its anomalies must be understood to achieve this. We reviewed the arteriograms of 100 patients who were potentially arterial perfusion candidates. Fifty percent had normal hepatic arterial anatomy. Twenty percent had a replaced or accessory right hepatic artery and 17% had an accessory or replaced left hepatic artery. The methods used to implant the pump catheters in these anomalous situations were reviewed. The use of dual catheter pumps for arterial anomalies has necessitated extended operative time and increased the risk of uneven hepatic perfusion. Catheterization of the portal vein, which is technically simpler, deserves consideration as an alternative in the presence of an aberrant arterial system.

Antineoplastic Agents↗
PubMed1985

Complications of pelvic exenteration.

This report is based on a retrospective review of 104 patients who had undergone pelvic exenteration for advanced malignancy over a 29-year period (1956 to 1984, inclusive). Fifty-one patients (49%) developed major complications of the operative field involving the gastrointestinal tract (fistula or obstruction), the urinary tract (fistula, infection, or obstruction), or the wound (abscess, dehiscence/necrosis, or hemorrhage). No association was identified between the complication rate and organ of primary disease, extent of disease, tumor histology, or extent of resection. Patients receiving pelvic radiotherapy prior to exenteration had a much higher complication rate (39/58, 67%) than patients having had no radiotherapy (12/46, 26%). Reconstruction of the irradiated pelvis after exenteration by omental flap, colonic advancement, and/or myocutaneous flaps decreased the complication rate from 82% (27/33) to 48% (12/25). The operative mortality of pelvic exenteration was 2.9% and the actuarial five-year survival rate was 27%.

Adolescent↗
PubMed1985

Inflammatory breast carcinoma: a distinct entity?

Sixty-four patients with the diagnosis of either inflammatory or locally advanced breast cancer were analyzed with respect to age, menopausal status, estrogen receptor protein (ERP) measurements, characteristics on clinical presentation, disease-free interval (DFI), and overall survival. There were no significant differences between the two groups in the patients' clinical presentation, DFI, or overall survival time. Patients with inflammatory carcinoma were significantly younger as well as more likely to be pre- or perimenopausal than patients with locally advanced breast cancer. Of those patients who had ERP measurements performed, patients with inflammatory breast cancer had a significantly decreased incidence of ERP(+) tumors in comparison to patients with locally advanced breast cancer. These results suggest that inflammatory carcinoma of the breast behaves as an ERP(-) subtype of locally advanced breast carcinoma rather than a truly distinct entity.

Adult↗