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Biomedical subjects

S G Economou

Publications and source records attributed to S G Economou.

At least 19 recordsLinked to original sources

Fibrin glue improves the healing of irradiated bowel anastomoses.

Many surgeons are reluctant to construct a bowel anastomosis with irradiated intestine. Previous studies have demonstrated diminished tensile strength of rat small bowel anastomoses that have been irradiated intraoperatively. To determine whether fibrin glue, a known tissue adhesive, improves the healing of these anastomoses, 69 male Sprague-Dawley rats were randomized into three anastomotic groups: Group 1, sutured ileal anastomosis without radiation or fibrin glue; Group 2, irradiated sutured ileal anastomosis without fibrin glue; and Group 3, irradiated ileal anastomosis with fibrin glue added to the suture line. Groups 2 and 3 received a single dose of 2,000 R intraoperatively. At seven days, the rats were sacrificed and the anastomotic segment was tested for breaking (tensile) strength. Anastomotic collagen content was evaluated using a hydroxyproline assay. Tensile strength results demonstrated that Group 2 was significantly weaker than Groups 1 and 3 (P = 0.001) and that the hydroxyproline content of Group 3 was significantly greater than that of Group 2 (P = 0.015). These results show that the addition of fibrin glue to an intraoperatively irradiated small bowel anastomosis improves healing, as demonstrated by both tensile strength and hydroxyproline content studies.

Anastomosis, Surgical

A prospective study of double diagnosis of nonpalpable lesions of the breast.

Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation.

Algorithms

Protection of fiber function by para-axial fluid flow in interstitial laser therapy of malignant tumors.

In the past, interstitial laser therapy frequently has failed because of the damage to the bare fiber tip due to intense heat generated at the point of contact. Using a rat mammary tumor model, we describe a method of placing a 600 micron fiber inside a gauge 19 needle cannula after its insertion into the tumor. With this device continuous wave Nd:YAG laser is delivered to the target tumor while 0.9% saline flows para-axially into the tumor. Significant coagulation necrosis was induced with 500 joules at 5 watts, 100 seconds and 1 cc per minute of saline while the needle-fiber is pulled out of the tumor by 10 mm. The mean transmission loss after 500 joules was 2% in ten experiments. The tumor edema due to 1.5 ml of saline was transient. We conclude that successful hyperthermic coagulation necrosis by Nd:YAG laser can be achieved with minimal transmission loss by employing the above technique.

Animals

Neuroendocrine differentiation in "poorly differentiated" colon carcinomas.

The diagnosis of "poorly differentiated" carcinoma was made in 47 of 683 colon cancers on the basis of conventional light microscopy which showed poorly defined glands, solid architecture or variable admixtures thereof. Samples from 44 of these 47 tumors were assessed by immunohistochemical analysis for the presence of neuroendocrine (NE) antigens. Paraffin sections were immunostained with antibodies to NSE, chromogranin, serotonin, VIP, substance P and somatostatin. Additional sections were also stained with monoclonal antibody (Mab) A-80 that recognizes a glycoprotein related to exocrine (EX) differentiation. Based on our findings, the tumors were phenotypically reclassified as follows: I) pure EX (n = 8), II) pure NE (n = 4), III) mixed EX-NE carcinomas (n = 23), and IV) predominantly EX carcinomas with occasional NE cells (n = 9). Survival among groups II and III appeared to be less than group I and survival in group IV was significantly less than group I. Survival among the four pure NE (group II) and 11 predominantly NE mixed carcinomas (group III) taken together was significantly less than the pure EX carcinomas. This study indicates: 1) The incidence of NE differentiation in tumors of the colon and rectum is higher than previously believed. 2) The poorly differentiated colon carcinomas comprise four distinct groups: pure EX, pure NE, mixed EX-NE carcinomas, and predominantly EX carcinomas with a NE cell subpopulation. 3) The presence of NE differentiation or of a NE cell subpopulation in colon carcinoma appears to be associated with a poorer prognosis.

Aged

Lymphokine-activated killer cell induction in tumor-infiltrating leukocytes from colon cancer patients.

Lymphokine-activated killer (LAK) cell induction was evaluated in the peripheral blood mononuclear cells (PBMC) from 28 colon cancer patients and in the tumor-infiltrating leukocytes (TIL) from 20 of the patients' colon cancer specimens. Modulation of LAK cell induction in TIL and PBMC by inhibitors of arachidonic acid metabolism also was examined. LAK cells were induced in vitro in isolated TIL and PBMC by culturing with 500 U/ml of recombinant interleukin-2 (IL-2) for 3 to 5 days, and this was followed by the assessment of cytolytic activity against natural killer (NK)-resistant Chang hepatoma cells. LAK cell induction in the TIL was depressed significantly, compared with LAK cell induction in the PBMC of colon cancer patients (P less than 0.01). In the majority of cases, indomethacin augmented LAK cell induction in the TIL (P = 0.073 for the entire group, compared with cultures not treated with indomethacin) and nordihydroguaiaretic acid (NDGA) depressed LAK cell induction (P less than 0.05 for the entire group, compared with cultures not treated with NDGA). Further characterization of the mechanisms responsible for modulating LAK cell induction in the TIL of cancer patients may identify ways to optimize their use in adoptive cellular immunotherapy.

Adult

Fine-needle aspiration biopsy of the thyroid. Diagnostic accuracy when performing a moderate number of such procedures.

The diagnostic accuracy of fine-needle aspiration biopsy of the thyroid was evaluated. Between June 1982 and July 1987, 354 fine-needle aspiration biopsies were performed on 289 patients with thyroid nodules. The ages of the patients ranged from 21 to 86 years (median, 45 years); 61 (21%) were men and 228 (79%) were women. Surgical confirmation of the cytologic diagnosis was obtained in 59 patients. Fine-needle aspiration biopsy identified 10% of the nodules as probably malignant and 10% as possibly malignant. Of these nodules, 30.5% were proved to be malignant by histologic examination. The accuracy of distinction between a benign (class I or II) or probably malignant (class IV) diagnosis was 95.2%. Patient acceptance of this procedure was good and complications were infrequent. These results indicate that fine-needle aspiration biopsy of the thyroid is accurate, safe, well tolerated, and easily applied, without its highly desirable features being compromised, even when a moderate number of such procedures are performed.

Adult

Primary retroperitoneal pure choriocarcinoma. Two long-term complete responders from a rare fatal disease.

Extragonadal germ cell tumors may have a worse prognosis than germ cell tumors of gonadal origin, even when tumor bulk and extent of dissemination are equal. Primary retroperitoneal pure choriocarcinoma is one of the least common subgroups of the extragonadal germ cell tumors and has previously appeared to have the worst prognosis. Two new case reports on the treatment and follow-up of two patients with primary retroperitoneal pure choriocarcinoma are discussed. Both patients are disease-free at 24 and 81 months, respectively. After aggressive primary multiagent drug therapy for primary retroperitoneal pure choriocarcinoma, a favorable prognosis may be anticipated.

Adult

The characterization of Ia+ cells in human parathyroid and islets.

Recent studies in animals have shown prolonged survival of endocrine allografts after treatment of the graft with Ia antibody prior to transplant. In this study, we documented the presence of Ia bearing passenger cells in human parathyroid and islets of Langerhans. Furthermore, we characterized these cells with regard to their expression of HLA-DQ and HLA-DR molecules using indirect immunofluorescence. We found that passenger cells in parathyroid express both HLA-DQ and HLA-DR. In contrast, islets express only HLA-DR. Parathyroid tissue treated first with polyclonal anti-DR or anti-DQ and complement eliminated cells that reacted with monoclonal anti-DR or -DQ probes, respectively. Similarly, islets treated with polyclonal anti-DR and complement eliminated cells that reacted with monoclonal anti-DR reagents. We believe that further characterization of Ia+ cells in human endocrine tissue will provide information that could be used to enhance allograft survival.

Cytotoxicity Tests, Immunologic

Carcinoma of the breast: detection with MR imaging versus xeromammography.

Detectability of breast cancer with magnetic resonance (MR) imaging versus xeromammography was quantitatively compared. MR images were obtained of breasts of 120 women who underwent xeromammography. T1 values were determined for masses larger than 2 cm. Cancer was histologically confirmed in 39 breasts and was considered excluded from 81 due to results of biopsy, cyst aspiration, or sonography or absence of change in xeromammographic findings over time. Images were blindly interpreted by three observers, and results were expressed as receiver operating characteristic curves. Detectability of breast cancer was substantially better with xeromammography than with MR imaging for all observers (P less than .03, 10(-6), and .001). On MR images, spiculation of a mass, distorted architecture, skin thickening, and nipple or skin retraction were specific but relatively insensitive indicators of cancer. Masses with smooth, distinct margins and signal intensity greater than that of fat on T2-weighted images were always benign. Other findings and T1 values were not diagnostically useful. The authors conclude that xeromammography is superior to MR imaging in detection of breast cancer.

Breast Diseases

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Adult

Sequential hormone therapy for advanced breast cancer.

Sequential hormone therapy for advanced breast cancer can offer significant and prolonged disease control with minimal morbidity. Predictors of response to sequential hormone therapy have not previously been identified. Sixty postmenopausal women with advanced or recurrent breast cancer treated with sequential megestrol acetate and tamoxifen were evaluated to identify factors which predict response to sequential therapy. The response rate to first-line therapy was 28% (17/60). Forty-seven percent of patients who responded to the first therapy responded to the second (8/17). Four of 16 patients (25%) who failed the first hormone therapy responded to the second. The response rate to a second hormone therapy was 25% (15/60). Chi-square tests were used to test the association between a response to sequential hormonal therapy and prior chemotherapy, age at first hormone trial, number of sites of disease, dominant site of disease, sequence of hormonal therapy, second response on the basis of first response, presence of soft tissue disease or bone disease alone, and receptor value. A one-tailed Fisher exact probability test revealed that a greater proportion of receptor-positive patients exhibited positive responses to sequential hormonal therapies than did receptor-negative patients. All of the patients who responded to a second hormonal therapy were estrogen receptor (ER)- and progestogen receptor (PgR)-positive. Fisher exact probability tests revealed a statistically significant association between response to initial hormone therapy and response to a subsequent hormone trial. This study suggests that patients who fail their initial hormone trial should be considered for a second hormonal trial if they are ER- and PR-positive.

Adult

Hormone receptor studies in axillary metastases from occult breast cancers.

The authors describe 11 patients with occult breast carcinoma, who initially presented with axillary nodal metastases of unknown origin. In all 11 cases, physical examination and mammography results were normal. Steroid hormone receptor studies were done on tissue from all 11 axillary masses and 2 masses underwent lactalbumin staining as well. In 8 of the 11 patients these studies were positive, suggesting breast as the primary tumor site. Estrogen (30 to 445 fmol/g) or progesterone (30 to 1059 fmol/g) receptors, or both, were positive in seven cases. Although a breast carcinoma was subsequently found in all 11 patients, receptor studies on the primary tumor could not be done in every instance. The authors concluded that performing steroid hormone receptor assays on axillary metastases from occult tumors not only may provide information regarding the identity of the primary tumor but also may be the sole opportunity to determine its hormone receptor status.

Adenocarcinoma

New method for cardiac transplantation.

Rat cardiac transplantation into the femoral region has several advantages compared to cardiac transplantation into the peritoneal cavity. These advantages include increased speed, decreased hypothermia of the recipient, and easier-access palpation. However, there is a major discrepancy in the size of the donor and recipient vessels. The donor aorta is two to three times larger than the recipient's femoral artery and thus could be a contraindication to the transplant. To circumvent this problem, we anastomosed the donor's aorta with the recipient's femoral artery by an end-in-end technique whereas the donor's pulmonary artery was anastomosed by conventional end-to-end technique with the recipient's femoral vein. The excess wall of the donor's vessel was plicated on a slant for each anastomosis. Our results compare favorably to those of techniques established previously. We suggest that this new method of cardiac transplantation will be of great value in the study of immunological events involved in graft rejection.

Anastomosis, Surgical

Bone scanning in pregnant patients with breast carcinoma.

Radionuclide scanning is usually contraindicated in pregnancy because of the danger of fetal radiation exposure. Radionuclide bone scanning with Tc-99m MDP is a sensitive indicator of early osseous metastases in breast cancer. Three cases of breast cancer during pregnancy are reported; modified bone scanning was utilized for staging and decision analysis. Modifications of bone scanning techniques to minimize fetal radiation exposure and fetal dosimetry calculations are described.

Abdomen

Extension of survival of rat parathyroid allografts by depletion of Ia donor cells plus preoperative cyclosporine.

Methods that avoid chronic immunosuppression of transplant recipients must be developed to eliminate the various risk factors associated with such treatment (e.g., increased infections and malignancies). Pretransplant treatment of the graft with anti-Ia serum plus complement to eliminate "passenger cells" is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for one week at 37 degrees C and treated with anti-Ia and complement. Treated glands were transplanted into parathyroidectomized, hypocalcemic Wistar-Furth recipients that had received 30 mg/kg of CsA once a day for the three days prior to transplant. At 1 year posttransplant, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected their grafts within 28 days. Controls given three days of CsA and transplanted with fresh, untreated glands all had functional grafts for greater than 56 days (median survival: 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given only at the time of antigen presentation. This course of CsA allowed for indefinite graft survival when the recipient received a graft previously cultured and treated with Ia antiserum. These results are encouraging and should be evaluated further to determine whether similar approaches will be useful in human transplants.

Animals

Indefinite survival of rat parathyroid allografts without postoperative immunosuppression.

Methods that avoid long-term immunosuppression must be developed for human parathyroid allotransplantation to be feasible. Pretransplant treatment of the graft to eliminate passenger cells is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for 1 week and treated with antiserum directed against class II major histocompatibility complex antigens. Treated glands were transplanted into hypocalcemic Wistar-Furth recipients that previously received 30 mg/kg of CsA once a day for 3 days before transplantation. At 280 days after transplantation, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected these grafts within 28 days. Control rats given 3 days of CsA and transplanted with fresh, untreated glands had functional grafts for greater than 56 days (median survival, 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given at the time of antigen presentation. This course of CsA is even more effective when the recipient receives a graft whose passenger cells are eliminated.

Animals

The role of ultrasonography in the evaluation of primary hyperparathyroidism.

Ultrasonography was used preoperatively in 21 patients with primary hyperparathyroidism in an effort to locate enlarged parathyroid glands. It indicated the presence of a solitary mass compatible with a parathyroid adenoma in 14 patients. At operation, adenomas were found at the location indicated by ultrasonography in 13 of the 14 patients (93 per cent). In seven patients, ultrasonography failed to reveal evidence of a mass of the parathyroid gland. At operation, three had diffuse parathyroid hyperplasia and four had a solitary adenoma. Of the four patients with adenomas undetected by ultrasonography, one patient had an adenoma which had undergone infarction and three had coexisting nodular thyroid gland disease. We concluded that ultrasonography is valuable in the preoperative assessment of patients with primary hyperparathyroidism. This is especially so in the absence of coexisting nodular thyroid gland disease. When positive, ultrasonography accurately locates adenomas, and when negative, it strongly suggests the presence of hyperplasia. This may have clinical application in limiting the extent of dissection and, thereby, reducing the morbidity of parathyroid gland exploration.

Adenoma

Megestrol acetate: first-line therapy for advanced breast cancer.

Megestrol acetate as initial hormonal therapy produced a 40% objective response rate in 53 patients with advanced breast cancer; another 26% achieved stable disease. For 19 patients with visceral-dominant disease, the response rate was 42%. To investigate the effect of the order of sequential hormonal therapy, records of 66 patients treated with tamoxifen before megestrol acetate or with megestrol acetate before tamoxifen were reviewed retrospectively. Of the 24 patients who were given megestrol acetate first, nine (38%) had objective response to primary therapy, and four (17%) to secondary therapy. Among the 42 patients treated with tamoxifen first, there were nine (21%) objective responses to primary therapy and eight (19%) responses to secondary therapy. Results show that megestrol acetate is effective first-line hormonal therapy for advanced breast cancer. Megestrol acetate can be used as primary hormonal therapy and tamoxifen as secondary hormonal therapy, as an alternative to the more usual reverse order. One may also consider megestrol acetate for some advanced breast cancer patients with visceral-dominant disease.

Antineoplastic Agents