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Biomedical subjects

A Sardi

Publications and source records attributed to A Sardi.

At least 55 records · Page 3Linked to original sources

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↗

The significance of mammographic findings after breast-conserving therapy for carcinoma of the breast.

Mammographic changes after lumpectomy, axillary dissection and irradiation are common and unpredictable. To study the significance of these changes at the first follow-up mammogram, we retrospectively reviewed reports of 172 women treated in this manner between 1979 and 1988. The mean follow-up time was 50 months. Eight patients had recurrences in the same breast, while 13 patients had carcinoma develop in the opposite breast. The mean time of follow-up mammograms was 11 months (range of one to 48 months). Twenty-six patients had a normal mammogram, while 146 patients had some changes within the irradiated breast. Thirty-one patients had suspicious findings--a mass, speculation or new microcalcifications. None of these 31 patients had carcinoma confirmed by biopsy or follow-up examination. Of eight patients with recurrence in the same breast, six had a biopsy because of findings on physical examination, while two had changes from previous mammograms. The mean time to recurrence was 50 months (range of 24 to 81 months). We conclude that mammographic changes in the irradiated breast are common after lumpectomy and irradiation for carcinoma of the breast. A baseline mammogram should be done six months after irradiation is completed. Changes that occur at this time should be considered secondary to surgical treatment and irradiation and are not an indication for immediate biopsy. These findings should be reconfirmed by a mammogram performed one year after irradiation to prove that these changes are stable. Physical examination and yearly mammography of both breasts are imperative in the follow-up evaluation of patients treated in this manner.

Adult↗

Improved survival after pulmonary resection of metastatic colorectal carcinoma.

While hepatic resection of metastatic colorectal carcinoma is accepted as effective in selected patients, resection of metastases to other solid organs has not gained wide acceptance. We retrospectively reviewed the records of 49 patients who had resection of isolated pulmonary (18 patients) and hepatic (31 patients) metastases from the large bowel, comparing disease-free survival and overall survival. Tumor parameters analyzed included Dukes' stage, deoxyribonucleic acid (DNA) flow cytometry, and number of metastases. Dukes' B and diploid tumors had longer disease-free survival and overall survival than did Dukes' C and aneuploid tumors, though the difference was not significant. Patients with a single lung metastasis had a significantly longer disease-free survival (P = .02) than did patients with multiple metastases. Mean and median survival were longer in patients with lung metastases. Five-year actuarial survival was 19% for patients with liver metastases and 47% for patients with lung metastases. Resection of isolated pulmonary metastases from the large intestine results in survival comparable to or better than resection of hepatic metastases. An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases of colorectal carcinoma.

Actuarial Analysis↗

Selective management of patients with neutropenic enterocolitis using peritoneal lavage.

Neutropenic enterocolitis is a symptom complex of fever, abdominal pain, distention, nausea, vomiting, diarrhea, and bloody stools occurring in a patient with a low neutrophil count and is most often seen in patients with acute leukemia after a course of chemotherapy. In most cases, neutropenic enterocolitis is a self-limited condition, but complications of transmural intestinal necrosis and bowel perforation may occur in a small number of patients. Surgical management should be reserved for those patients with bowel wall necrosis or perforation; however, early identification of these patients is difficult. We report our experience with the use of diagnostic peritoneal lavage in three patients with the symptoms and signs of neutropenic enterocolitis. In each case, Gram's stain of lavage fluid revealed no evidence of polymicrobial contamination of the peritoneal cavity. All three patients were managed medically, with resolution of their abdominal symptoms. Peritoneal lavage is helpful in excluding bowel perforation and avoiding unnecessary surgical intervention in patients with neutropenic enterocolitis.

Adult↗

Prognostic value of DNA flow cytometry in thymomas and thymic carcinomas.

Thymomas are the most common anterior mediastinal masses. Malignant potential and prognosis are unrelated to histologic appearance. Deoxyribonucleic acid (DNA) flow cytometry is of prognostic significance in a variety of tumors. We reviewed the records of 35 patients who on pathologic examination had a thymoma or thymic carcinoma. Flow cytometric studies, including DNA indices (ploidy) and S phase fraction, were done on paraffin block specimens from 31 patients. We believe this is the first report of DNA flow cytometric studies in thymic pathology. Mean survival was 63.5 +/- 13.3 months for patients with benign thymomas, 10.5 +/- 4.6 months for patients with malignant thymomas, and 19.3 +/- 4.1 months for patients with thymic carcinomas. Patients with benign thymomas lived significantly longer than those with malignant thymomas (P = .001) and thymic carcinomas (P = .03). DNA flow cytometry demonstrated four aneuploid tumors (two benign thymomas and two malignant thymomas). All thymic carcinomas were diploid. There was no statistically significant difference among the groups. The mean S phase fraction was 15.22% for benign thymomas, 11.15% for malignant thymomas, and 14.31% for thymic carcinomas. No statistically significant difference was found among the groups. We conclude that flow cytometry is not a useful guide to malignant potential or prognosis in thymomas and thymic carcinomas.

Analysis of Variance↗

Urachal abnormalities in adults: the Ochsner experience.

Urachal abnormalities are very rarely encountered in adults. Though the urachus is normally obliterated in early infancy, it may cause a lower midline lesion in adults. Urachal abnormalities can be classified into five groups: patient urachus, urachal sinus, vesicourachal diverticulum, urachal cyst, and alternating sinus. The medical records of Ochsner Medical Institutions were reviewed for the 31-year period 1957 to 1988. Forty-one patients were identified as having anomalies of the urachus, 11 of them in the adult age group (older than 17 years). All cases were documented by pathologic examination. All patients were treated surgically, with no resultant morbidity or mortality.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

Localization by hand-held gamma probe of tumor labeled with antibody "cocktail".

Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.

Adenocarcinoma↗

An assessment of prolonged reactivity of seven monoclonal antibodies against CX-1 tumor xenografts using a hand-held gamma-detecting probe.

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.

Adenocarcinoma↗

Staging of carcinoma of the breast using a hand-held gamma detecting probe and monoclonal antibody B72.3.

Radioimmunoguided Surgery (RIGS) uses a hand-held gamma detecting probe to identify radiolabeled monoclonal antibodies (Mab). Fourteen patients with carcinoma of the breast proved at biopsy received Mab B72.3 (5 millicuries of 125I per 1 milligram, Iodo-Gen method) intravenously six to 26 days before exploration. Probe counts were measured intraoperatively in mammary tissue and axillary lymph nodes. In the mammary tissue, the RIGS system identified tumor that was histologically confirmed in seven of eight patients and confirmed the absence in four of six patients. Probe counts were suspicious for tumor that was not proved histologically in two of 14 patients. Unsuspected tumor was identified in three of 14 patients. In axillary tissue, probe counts identified one of two tumors that were confirmed histologically and verified the absence of tumor in eight of 12 patients. Probe counts in axillary tissue were suspicious for tumor that could not be documented histologically in four of 14 patients. RIGS appears to be able to identify residual, subclinical and multicentric carcinoma of the breast and accurately delineate the pattern of antigenic drainage of tumor into adjacent lymph nodes.

Antibodies, Monoclonal↗

Radioimmunoguided surgery in recurrent colorectal cancer: the role of carcinoembryonic antigen, computerized tomography, and physical examination.

From January 1986 to December 1987, 32 patients with recurrent colorectal cancer had second-look radioimmunoguided surgery (RIGS system). All patients had pathologic confirmation of recurrence. The RIGS system identified 81% of recurrences, and in six patients recurrent tumor was identified only by RIGS. All patients had physical examination, carcinoembryonic antigen (CEA) assay, and computerized tomography of the abdomen and pelvis. Detection of recurrence was based on symptoms in six, elevated CEA value in 25, and physical examination in one. The CEA was elevated preoperatively in 30 patients; two false-negative results occurred in symptomatic patients who had pelvic recurrence. The median CEA value in those with liver recurrence was 30 ng/ml (range 5.2 to 298) and for pelvic recurrence 13 ng/ml (range 1.9 to 31) (P less than .05). The overall sensitivity of CT was 41% (abdomen other than liver 37%, liver 56%, and pelvis 22%). The combination of elevated CEA, symptoms, and physical findings identified 100% of recurrences. We conclude that a rising CEA remains the most accurate indicator of recurrence. CT should not be done routinely to detect recurrent colorectal cancer unless CEA is elevated or the patient is symptomatic. In our study the intraoperative use of the RIGS system aided the surgeon in identifying occult tumors.

Adolescent↗

Multiple reoperations in recurrent colorectal carcinoma. An analysis of morbidity, mortality, and survival.

Fifty-eight patients in an existing prospective study were evaluated to determine if multiple reoperations for recurrent colorectal carcinoma extended survival. All patients had at least three major operative procedures. The median survival from first, second, third, fourth, and fifth recurrence was 29.9, 17.3, 16, 12.3, and 7.2 months, respectively. The median postoperative hospital stay was 11 days, with a range of 1 to 96 days. The major complication rate was 17%. Twenty-one patients are still alive 19 to 140 months from diagnosis (mean, 50.3 months), 9 to 125 months from the first recurrence (mean, 31.1 months), and 5 to 109 months (mean, 22 months) from the second recurrence. Eleven patients have no evidence of disease. Reoperation for recurrent colorectal carcinoma can be done with acceptable morbidity and mortality and an increase in survival.

Adult↗

Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects.

The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.

Adult↗