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Biomedical subjects

E W Martin

Publications and source records attributed to E W Martin.

At least 19 recordsLinked to original sources
PubMed1992

Intraoperative detection of colorectal cancer with radioimmunoguided surgery and CC49, a second-generation monoclonal antibody.

Radioimmunoguided surgery (RIGS) has been employed intraoperatively in cases of colorectal cancer to assess the extent of local tumor spread and metastatic disease. This technique uses radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens, and a hand-held gamma-detection probe to detect the radiolabel fixed to tumor tissue. Recently introduced is an MAb directed against tumor-associated glycoprotein (anti-TAG), CC49. Sixty patients were entered into the initial study. Eighteen of 21 (86%) primary tumors were localized by the CC49 MAb and the gamma-detecting probe. Twenty-nine of 30 (97%) recurrent tumors were localized. Antibody dose did not affect localization. Specimens were divided into tissue types I through IV, based on antibody localization and hematoxylin and eosin (H&E) staining: type I, RIGS (-) and histologically (-); type II, RIGS (-) and histologically (+); type III, RIGS (+) and histologically (-); type IV, RIGS (+) and histologically (+). Type IV tissue were further classified by whether they were grossly apparent, IVa, or grossly inapparent, IVb (occult). Occult tumor found by RIGS and confirmed by H&E staining (type IV) had localization ratios similar to RIGS-positive, histology-negative tissue (type III). Traditionally found cancer (type IV) had significantly higher ratios. In 12 of 24 patients (50%) with primary tumors and 14 of 30 patients (47%) with recurrent tumors, RIGS with CC49 altered the planned operative procedure. Radioimmunoguided surgery with CC49 provides useful, immediate intraoperative information not available by other techniques.

Adult↗
PubMed1992

Radioimmunoguided surgery challenges traditional decision making in patients with primary colorectal cancer.

BACKGROUND: Initial experience with the radioimmunoguided surgery system (RIGS) has been found to impact on decision making in patients with recurrent colorectal cancers. Reported here is experience with RIGS-influenced therapeutic decisions in patients with primary colorectal cancer. METHODS: Thirty-six evaluable patients with primary cancers were injected with the second-generation anti-tumor-associated glycoprotein antibody CC49 labeled with 1 to 2 mCi iodine 125. Pharmacokinetic determination and precordial counts were obtained after injection and weekly until levels were less than 20 counts/2 sec. At surgery abdominal and pelvic explorations were performed, first traditionally by inspection and palpation and then with the hand-held, gamma-detecting probe. RIGS-positive tissue was considered cancerous and removed if possible. RESULTS: Thirty patients (83%) had positive antibody localization at surgery. Of those patients with localization, in 24 (80%) additional information was obtained at the time of surgery. In 11 patients (34%) staging changes were made as a result of RIGS exploration. New findings resulted in operative changes in nine patients (25%). Eleven (30%) of the original 36 patients became eligible for adjuvant chemotherapy based on current recommendations because of RIGS findings. CONCLUSIONS: In conclusion, the RIGS system provides immediate staging information that impacts on therapeutic interventions, challenging the adequacy of traditional procedures alone for primary colorectal cancer exploration.

Colonic Neoplasms↗
PubMed1991

Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer.

Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.

Antibodies, Monoclonal↗
PubMed1991

Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas.

Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN-gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1991

Second-look surgery for colorectal cancer. The second time around.

Eighty-six colorectal cancer patients who entered the Radioimmunoguided Surgery (RIGS) protocol study were evaluated for 2-, 3-, 4-, and 5-year survival following second-look surgical procedures. Strict preoperative evaluation criteria eliminated patients with extra-abdominal tumor involvement. A saturated potassium iodide preparation was given before the intravenous administration of the B72.3 monoclonal antibody (1 mg) radiolabeled with 2 mCi of iodine-125 by the IODOGEN method. Precordial monitoring of the biologic clearance by the handheld, gamma-detecting probe (Neoprobe 1000 instrument) was conducted at weekly intervals until the average count was less than 20 counts in 2 seconds. Once the drug cleared from the blood, surgery was performed. The mean time interval between injection and operation was 24 days, with a range of 21 to 28 days and a median of 23 days. At surgery the abdomen was explored through the traditional methods of palpation and inspection, and the surgeon committed to a planned procedure. The abdomen was then re-explored with the handheld, gamma-detecting probe and the surgeon stated another intraoperative assessment. After using both traditional and RIGS detection methods, the surgeon stated whether his or her surgical plans changed because of the additional intraoperative information provided by the RIGS system. Fifty-three patients (62%) were deemed resectable by the traditional methods of palpation and inspection, but only 40 (47%) were specified as resectable by RIGS exploration. Two-, three-, four-, and five-year survival data could be gathered for each of the three groups: RIGS resectable (n = 40), traditional nonresectable (n = 33), and RIGS nonresectable (n = 13). At 2 years 95% of the resectable, 36% of the traditional nonresectable, and 53% of RIGS nonresectable patients survived. At 3 years 83%, 7%, and 30% of these patients survived, respectively. For the resectable patients, 74% survived at 4 years and 60% at 5 years, with no survivors from either nonresectable group. Use of the RIGS system increased accurate selection of resectable patients undergoing second-look surgery for recurrent colorectal cancer.

Antibodies, Monoclonal↗
PubMed1991

Second hepatic resection for metastatic colorectal cancer.

We report a case where repeat hepatic resection was successfully performed 3 years after extended right hepatic lobectomy for metastatic colorectal cancer. The patient remains well and disease free 2.5 years after the second hepatic resection.

Adenocarcinoma↗
PubMed1991

Radioimmunoguided surgery (RIGS) in recurrent colorectal cancer.

Since 1986, 191 patients with recurrent colorectal cancer have undergone surgical exploration 2 to 43 days after injection of 1.0 to 0.25 mg of monoclonal antibody (MAb) (B72.3 or 17-1A) radiolabeled with 5.0 to 1.0 mCi of 125I. The intraoperative use of a hand-held gamma detector (Neoprobe 1000) demonstrated that MAb identified tumor in 73% of cases. Clearer intraoperative definition of tumor margins and identification of occult tumor assisted the surgeon in the resection of liver metastases as well as nodal and pelvic disease. Unsuspected nodal disease was identified. The external use of the Neoprobe to scan the sacral region and intrarectal and intravaginal use led to the avoidance of operative procedures by defining inoperable disease. In approximately 25% of cases, the surgical procedure was modified based on Neoprobe findings. RIGS system provides a method of immediate intraoperative staging which may prevent additional recurrences, lead to earlier institution of adjuvant therapy, and result in improved survival.

Antibodies, Monoclonal↗
PubMed1990

Gamma-detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX-1 colon xenografts.

Nude mice bearing CX-1 colon tumors were injected with 50 microCi 125I-labeled monoclonal antibody (MAb) B72.3. Radioactivity in tumors was studied with the gamma detecting probe (GDP) on days 1, 3, 7, and 10 after MAb injection. On each day, two mice were sacrificed and sections were examined with autoradiography (ARG), immunoperoxidase methods (IMP), and routine stains. Mean probe counts showed increasing tumor to background ratios and ARG demonstrated a progressive increase in radionuclide in the tumors. The distribution of 125I was primarily around the vascular spaces on day 1, but by day 3 and progressively it appeared in tumor gland lumina and necrotic areas. A regional correlation was shown between radionuclide in vascular spaces and its sequestration in tumor elements.

Animals↗
PubMed1990

Radioimmunoguided surgery in primary colon cancer.

Radioimmunoguided surgery (RIGS), the intraoperative use of a hand-held gamma detecting probe (GDP) to identify tissue containing radiolabeled monoclonal antibody (MAb), was performed upon 30 patients with primary colon carcinoma. Each patient received an intravenous injection of MAb B72.3 (1.0 to 0.25 mg) radiolabeled with 125I (5.0 to 1.0 mCi) 8 to 34 days before exploration. The GDP was used to measure radioactivity in colon tissue, tumor bed, nodal drainage areas, and areas of suspected metastases. Antibody localized to histologically documented tumor in 23 of 30 patients (77%). Tumor margins were more clearly defined in 20 of 30 patients (67%). GDP counts led to major alterations in surgical resection in five patients (17%) and changes in adjuvant therapy in four (14%). GDP counts identified occult liver metastases in two patients (7%) and correctly indicated the benign nature of liver masses in three (10%). In four patients (13%), occult nodal metastases were identified. RIGS can precisely delineate tumor margins, define the extent of nodal involvement, and localize occult tumor, providing a method of immediate intraoperative staging that may lessen recurrences and produce higher survival rates.

Antibodies, Monoclonal↗
PubMed1990

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↗
PubMed1989

Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system).

Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences.

Abdominal Neoplasms↗
PubMed1989

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↗
PubMed1989

The impact of radioimmunoguided surgery (RIGS) on surgical decision-making in colorectal cancer.

Radioimmunoguided surgery (RIGS system) was performed in ten patients with rectal or low sigmoid colon carcinoma with the use of a hand-held gamma detector (Neoprobe 1000) intraoperatively and externally after injection of radiolabeled (125I) monoclonal antibody to detect pelvic and metastatic tumor. Fifteen procedures, including six exploratory laparotomies, four transperineal explorations, two transsacral explorations, one transvaginal biopsy, one brachytherapy, and one transanal polypectomy, were performed. Two patients had previous low anterior resection, seven abdominoperineal resection, and one a rectal polypectomy. Five patients had previous pelvic radiation therapy. Reoperation was indicated by elevated CEA levels in seven patients (70 percent), persistent pelvic pain in six (60 percent), and a suspicious radiologic study in seven (70 percent). RIGS system localized tumors verified by histopatholoy in all ten patients (100 percent); one patient with a positive CT scan and probe findings lacked histopathologic confirmation on frozen section, but had a tumor confirmed on permanent histology. Five major abdominal operations were avoided; in five patients major modifications were made in the surgical procedure based on probe findings. Six received chemotherapy or radiation therapy based on findings of the RIGS system. In six patients with negative or equivocal CT scans, the RIGS system localized histopathologically confirmed tumor. Major abdominal procedures can be avoided, the surgical approach modified, and other modes of therapy instituted earlier with the use of the RIGS system.

Aged↗
PubMed1989

Solving the problem of antibody interference in commercial "sandwich"-type immunoassays of carcinoembryonic antigen.

We evaluated the effect of human anti-murine antibodies (HAMA) on apparent concentrations of carcinoembryonic antigen (CEA) as measured in serum with commercial enzyme immunoassay (EIA) kits manufactured by Abbot ("two-step" double monoclonal antibody assay), Roche, and Hybritech (room-temperature protocol). In sera from patients given parenteral murine monoclonal antibody for experimental diagnostic and immunotherapy studies, HAMA titers were determined with Immunomedics' "ImmuSTRIP HAMA-EIA" kit reagents. "True" CEA titers were established by using the ImmuCEA/MA-EIA and heat-extraction to destroy HAMA before assay for CEA. The concordance of the ImmuCEA/MA assay with the Abbott and Roche CEA EIAs was established with sera from normal individuals and from patients who had not received parenteral injections of murine monoclonal antibody. At high (100 mg/L) concentrations of HAMA, false-positive results were observed with all three kits. The Hybritech and Roche assays were more sensitive to interference by HAMA than was the Abbott CEA-EIA, false-positive results being observed at HAMA concentrations between 1 and 10 mg/L. Similar sensitivity of the three kits to interference by primate anti-MAb sera was demonstrated. Use of primate anti-MAb sera to create controls with HAMA activity and of analyte is recommended to evaluate MAb assays for potential HAMA interference and for use to devise methods to eliminate HAMA interference.

Animals↗
PubMed1989

Symptom management in the home-based terminal cancer patient.

Comprehensive symptom management is the hallmark of good medical care of the terminally ill cancer patient. Careful attention to patient comfort and early assessment and intervention to alleviate distressing symptoms enable the patient to remain at home, and maximize the quality time which the patient and family can share.

Home Care Services↗