Biomedical subjects

H F Seigler

Publications and source records attributed to H F Seigler.

At least 127 records · Page 7Linked to original sources

PubMed1985

Carcinoma of the pancreas. Therapeutic efficacy as defined by a serodiagnostic test utilizing a monoclonal antibody.

DU-PAN-2 is a high molecular weight glycoprotein defined by a murine monoclonal antibody elicited to a pancreatic ductal adenocarcinoma cell line. This monoclonal antibody recognizes an oncofetal antigen present on the surface of pancreatic tumor cells. The antigen has also been detected in the sera of patients with adenocarcinoma of the pancreas by a competition radioimmunoassay (RIA). Ninety-four per cent (31/33) of patients with pancreatic adenocarcinoma in this study had DU-PAN-2 serum antigen levels greater than 300 units/ml by RIA, whereas sera from normal adults had serum levels less than 300 units/ml. Serial studies of DU-PAN-2 serum antigen in pancreatic cancer patients with elevated DU-PAN-2 serum levels (mean: 2873 units/ml) and surgically resectable neoplasms demonstrated a return to the normal range within 1 to 3 weeks after surgery in five of six patients. Five patients in clinical remission had normal DU-PAN-2 serum levels (mean: 110 units/ml). With tumor progression, however, the DU-PAN-2 level increased in all patients (mean: 2835 units/ml) an average of 2 months before evidence of progressive disease by clinical parameters. Serial DU-PAN-2 determinations are sensitive monitors of the progression of pancreatic cancer and may be useful as early indicators of response to therapy.

Adenocarcinoma↗

PubMed1985

Long-term clinical outcome of immediate reconstruction after mastectomy.

Immediate reconstruction of a breast removed for treatment of carcinoma can be accomplished without altering the cancer-ablative surgical procedure. The theoretical possibility that reconstruction might compromise the cure rate has tempered enthusiasm for this approach. To test this issue, the relapse-free survival of 101 patients who underwent breast reconstruction in the immediate postmastectomy period was compared with that of 377 patients with breast cancer who underwent mastectomy without immediate reconstruction. This comparison was accomplished using multivariable statistical techniques to correct for baseline inequalities between the patient groups. After adjustment for the relevant prognostic factors, no significant difference remained between the two groups. We conclude that immediate reconstruction has no discernible adverse influence on the natural history of surgically treated breast carcinoma.

Adult↗

PubMed1985

Expression of a melanoma-tumor-associated antigen as demonstrated by a monoclonal antibody (D6.1) in cytopathologic preparations of human tumor cells from effusions and needle aspirates.

Immunocytopathologic studies were performed on 79 fine needle aspiration biopsies (FNABs) and effusions from 13 melanomas and 57 other human neoplasms with the monoclonal antibody (MAb) D6.1 raised against a partially purified melanoma-tumor-associated antigen (MTAA). The purposes of these studies were (1) to evaluate the ability of MAb 6.1 to react with melanoma cells in cytopathologic preparations and (2) to define the spectrum of reactivity of MAb D6.1 in cytopathologic preparations of non-melanomas. Cytocentrifuge preparations of the cytopathologic specimens were permitted to react with the primary antibody and were then stained by the avidin-biotin-immunoperoxidase method. Thirteen of 13 FNABs of malignant melanomas exhibited staining reactivity with MAb D6.1. Among the nonmelanoma tumors tested, staining reactivity was observed in 30 of 57 specimens. Among specific neoplasms, staining was present in 5 of 11 adenocarcinomas of the breast, 2 of 7 ovarian adenocarcinomas and 5 of 6 metastatic adenocarcinomas from the colon. Among 17 lung cancers examined, staining was noted in 4 of 7 adenocarcinomas, 3 of 4 large-cell undifferentiated carcinomas and 2 of 3 poorly differentiated squamous-cell carcinomas. Two small-cell undifferentiated carcinomas and one carcinoid failed to stain. Three of three adenocarcinomas of the pancreas showed staining. Among the remaining neoplasms examined, one specimen each of carcinoma of the prostate and the cervix and one carcinoma of undetermined primary exhibited staining. Two malignant lymphomas did not stain. Staining of mesothelial cells was observed in three of nine benign effusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1984

Detection of a pancreatic cancer-associated antigen (DU-PAN-2 antigen) in serum and ascites of patients with adenocarcinoma.

A competition radioimmunoassay was developed, utilizing a murine monoclonal antibody to human pancreatic adenocarcinoma cells. Immunoblotting of a standard antigen preparation from either serum or ascites fluid after electrophoresis in 1% agarose showed that the specific DU-PAN-2 activity resided in two major high molecular weight bands. DU-PAN-2 antigen levels were expressed as arbitrary units based on a standard partially purified antigen preparation. The inhibition curve with standard antigen was reproducible (SD less than 10%) and essentially linear from 25 to 200 units/ml. The mean DU-PAN-2 antigen concentration for the sera from 126 normal individuals was 81 units/ml. Sera from pediatric patients with malignancy had a mean of 127 units/ml, while nasopharyngeal, stage III melanoma, and ovarian carcinoma patients had means of 89, 92, and 119 units/ml, respectively. All values in normal subjects as well as the melanoma, nasopharyngeal, ovarian, and pediatric cancer patients were less than 400 units/ml. Intermediate antigen levels were detected in patients with alimentary tract malignancies. Eight of 20 gastric cancer and 8 of 76 colorectal carcinoma patients and 3 patients with benign or nonmalignant gastrointestinal tract disease had DU-PAN-2 values exceeding 400 units/ml. Ascites fluids from 6/6 and pancreatic juice from 2/2 pancreatic cancer patients had values greater than 750 units/ml. Serum from 68% of the 89 pancreatic cancer patients tested had DU-PAN-2 antigen levels greater than 400 units/ml. The mean serum value in this patient population was 4888 units/ml.

Adenocarcinoma↗

PubMed1984

D6.1, a murine antimelanoma monoclonal antibody from congenitally athymic nude mice immunized with purified melanoma tumor-associated antigen.

An IgM monoclonal antibody, D6.1, has been obtained by fusion of P3 X 63Ag8.653 with spleen cells from congenitally athymic nu/nu mice immunized with partially purified human melanoma TAA bound to insolubilized lens culinaris lectin. The D6.1-defined antigen is present on the cell membrane of melanoma cells maintained in tissue culture but is not detected in spent culture media. Eighteen of twenty-three melanoma cell lines tested were found to react with D6.1, in contrast to only 17% of nonmelanoma tumor cell lines. Among those reactive nonmelanoma tumor lines were 3/3 colon adenocarcinomas tested. Melanoma cells, in general, express greater quantities of this antigen than do reactive nonmelanomas. Similar data were obtained using immunoperoxidase techniques on frozen sections of fresh tumor. All melanomas tested (8/8) stained intensely, although there was tumor cell heterogeneity. D6.1 reacted, but generally less intensely, with 42% (18/42) of the nonmelanoma tumors tested, including 7/8 colon carcinomas, but with smaller percentages of all other tumor types. D6.1 lightly stained normal stroma in many tissues and reacted strongly with macrophages but not with epithelial tissues. By HPLC filtration, the D6.1-defined TAA from detergent-solubilized melanoma cell membranes was determined to have an apparent molecular weight of 150,000 to 280,000 daltons. D6.1 does not precipitate TAA from exogenously (125I) or endogenously (35S-methionine, 33H-leucine, 33H-glucosamine) labeled melanoma cells.

Adenocarcinoma↗

PubMed1984

Radiologic, endoscopic, and surgical considerations of melanoma metastatic to the gastrointestinal tract.

Malignant melanoma is the most common malignancy to metastasize to the gastrointestinal tract. In a retrospective computer-assisted data search of over 2500 patients with melanoma registered over the past 10 years, 110 patients have been identified to have premortem gastrointestinal metastatic disease (metastatic disease identified at least 6 months before death). The small intestine (35%), colon (14.5%), and stomach (7%) are the most common sites for metastases. Polypoid or ulcerating masses and intramucosal nodules are typical radiologic presentations for gastric and colonic lesions, while over 50% of the small bowel metastases are polypoid masses that many times act as leading points for intussusception. Endoscopic studies are helpful in the preoperative diagnosis of these lesions. In a subset of 38 patients with symptomatic small bowel metastatic disease, complete resections were performed in 26% of patients, with palliative bypasses being performed in 40%, despite the fact that over 50% of the patients had documented visceral metastasis in other body sites. The operative morbidity rate was 15% with no operative deaths. Ninety percent of patients gained relief of symptoms, and overall survival from the time of confirmed small bowel disease averaged 17.3 months, with a range of 6 months to 9 years. It would seem that patients with melanoma with gastrointestinal metastatic disease can benefit from aggressive radiologic and endoscopic procedures for diagnosis and staging. Only through surgical interventions for symptomatic gastrointestinal disease can the quality of life be improved and life expectancy be extended.

Colonic Neoplasms↗

PubMed1984

Sex related survival differences in instances of melanoma.

While data concerning melanoma survival differences between the sexes as they relate to anatomic site, stage and age is scattered throughout the literature, few single studies on one large population of patients with melanoma have specifically addressed all the confounding variables proposed to account for such sex related survival differences. Data were collected for 1,489 patients with melanoma observed at Duke University Comprehensive Cancer Center. Females had a more favorable prognosis than males. This survival difference could not be fully explained by differences in the anatomic site of the primary, Clark level of invasion, histologic type or ulceration of the primary lesion or age at diagnosis between males and females. There is growing epidemiologic and biochemical evidence that melanoma may be affected by sex hormones.

Adolescent↗

PubMed1984

[In vivo evaluation of cellular immunity in melanoma patients against melanoma].

Evaluation of cellular immunity against human melanoma was performed in an in vivo model using Balb/c nude mice bearing the human melanoma. Intraperitoneal injection of 1 X 10(7) melanoma cells produced peritonitis carcinomatosa which lead to death of the mice at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from healthy donors and the melanoma cells cultured on the back of the nude mouse were given to nude mice intraperitoneally, and survival times of 22.0 +/- 2.3 days were observed (N = 8). PBL from four of the five healthy donors which have been presensitized on monolayers of the melanoma tissue culture cells in flask failed to prolong host survival times. In contrast, PBL from 15 of 20 melanoma patients were found to prolong the survival of the tumor bearing nude mice. Of these 15 patients, 8 were treated with specific active immunotherapy, but 7 had not been sensitized except by the disease process. The ability of PBL from patients to prolong survival of the melanoma bearing nude mice did not seem to correlate with either the stage of the disease or the clinical course. The possible mechanisms for the prolonged survival and the usefulness of this in vivo model were discussed.

Animals↗

PubMed1983

Cutaneous melanoma of the head and neck. A review of 399 cases.

A retrospective search of the Duke University Melanoma Clinic patients identified 399 cases with primary malignant melanoma located in the head and neck region. Ninety-five percent of the deaths in this series were from metastatic melanoma. Various clinical and pathological data were examined and their effects on survivability and disease-free intervals were evaluated. The characteristics noted included sex, age, depth of the invasion, thickness, site of the lesion, histologic type, and nodal status. A multivariate regression analysis identified the following factors as having a negative effect on survival: nodular histologic type, scalp primary, increasing Clark level, and male sex. In comparing head and neck, extremity, and truncal primary sites, the median survival for patients with head and neck malignant melanomas was notably less. These differences correlated with a higher incidence for male patients, for patients with thicker lesions, and for patients with an increased frequency of nodular histologic type.

Adolescent↗

PubMed1983

Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5.

Recently a murine monoclonal antibody (A2B5) has been described that reacts with a membrane associated GQ ganglioside common to peptide secreting normal cells and tumors. In vitro binding data demonstrated the presence of this ganglioside on neurons, adrenal medulla, and pancreatic islets, along with neuroendocrine tumors such as insulinomas, pheochromocytomas, melanomas and neuroblastomas. Negative binding has previously been shown for tissue sections from liver, kidney, colon, lung, stomach, and tumors not derived from the neural crest. Because of the specificity at A2B5 in vitro, this monoclonal antibody was labeled with 131I for in vivo tumor localization studies. Daily radionuclear scans were obtained in 5 KX rats bearing the radiation induced rat insulinoma with disappearance of the label from the blood pool and concentration in the tumor so that by the fourth day, the only activity present by scan was in the insulinoma. Tissue-counting data showed tumor/blood ratios (av +/- SE, 1.29 +/- 0.25) of A2B5 activity two to ten times the average activity found in other organs (0.28 +/- 0.05). No tumor concentration of the control nonspecific monoclonal antibody P3X63 was evident (0.27 +/- 0.04). In addition A2B5 also localized to five different human melanoma cells lines grown in nude mice with high tumor/blood levels (1.04 +/- 0.27) compared to normal tissues (0.32 +/- 0.05) (P = .0005), while no localization is seen in nudes carrying osteosarcomas, colon, bladder, and renal cell carcinomas. In addition antibody A2B5 did not concentrate in any normal tissue though the antigen is present on several. The finding that A2B5 reacts across species lines (mouse, rat, man) lends itself to obvious diagnostic and therapeutic possibilities.

Adenoma, Islet Cell↗

PubMed1983

Efficacy of elective lymph node dissection in patients with intermediate thickness primary melanoma.

One of the most controversial areas in the management of malignant melanoma concerns the efficacy of prophylactic lymph node dissection. During a retrospective computer-aided data review of over 3000 melanoma patients referred to the Duke University Cancer Center, 613 patients with complete staging along with surgical and pathologic data, having trunk and extremity melanoma, were identified with Breslow thickness in the range of 0.76 to 4.0 mm. One hundred eighty-seven of these clinically node-negative patients received an elective lymph node dissection (WLE/ND). The remaining patients were treated only with an initial wide local excision (WLE) at the time of diagnosis of their melanomas. There was no difference in age at diagnosis or male-female ratio between the treatment groups. A higher percentage of the WLE/ND group (36% vs. 31%) showed ulceration of their primary lesions and a greater mean tumor thickness (1.81 +/- 0.80 mm vs. 1.60 +/- 0.73 mm) than the WLE patients. Despite the force of these two adverse prognostic factors in the WLE/ND group, only ten deaths (5%) have occurred in the elective lymph node group compared to 51 (12%) in the control group. Using a multifactorial analysis to control for the prognostic contribution of the two most informative variables in stage I melanoma, Breslow thickness and ulceration, WLE/ND had an independent favorable effect on survival (p = 0.01). There was no apparent additional benefit to lymph node dissection in patients whose primary lesion measured less than 0.76 mm or greater than 4.0 mm in thickness. The surgeon may use survival estimates with and without elective node dissection based on a prognostic equation ("prognostigram") as a quantitative aid to treatment planning.

Actuarial Analysis↗

PubMed1983

Application of posterior neck dissection in treating malignant melanoma of the posterior scalp.

Utilization of a posterior neck dissection in the treatment of nine patients with malignant melanoma of the posterior scalp is presented. Seven of nine patients presented with metastatic disease present in the posterior neck after initial treatment elsewhere. Four of the seven patients developed regional disease 4 months to 4 years following initial diagnosis. Variables dictating surgical treatment included the Clark's level, Breslow depth of invasion of original lesion, evidence of metastatic disease, and type of melanoma. The surgical technique of the posterior neck dissection is graphically depicted and the indications outlined. The posterior neck dissection is mandatory to adequately resect the primary lymphatics of the posterior scalp. Controlled studies are urged to determine the efficacy of prophylactic surgical lymphadenectomy in malignant melanoma of the head and neck.

Adult↗

PubMed1983

Solitary pulmonary metastases in high-risk melanoma patients: a prospective comparison of conventional and computed tomography.

A prospective comparison of chest radiography, conventional tomography, and computed tomography (CT) in the detection or confirmation of solitary pulmonary nodules was made in 42 patients with high propensity for pulmonary metastases due to advanced local (Clark level IV or V) or regional malignant melanoma. Unequivocal nodules were revealed by chest radiography in 11 patients, conventional tomography in 16, and computed tomography in 20 patients. Both plain films and tomography in three of these 20 were normal, but follow-up verified pulmonary metastases. Computed tomography detected more pulmonary nodules than conventional tomography in 11 patients in addition to identifying lesions in extrapulmonary sites. Therefore, chest CT is recommended before institution of immunotherapy or surgical removal of a solitary pulmonary melanoma metastasis. Once chemotherapy had been instituted for bulky regional or cutaneous involvement, however, the findings of either conventional or computed tomography were comparable in this study.

Adult↗

PubMed1983

Transplantation of rat insulinoma allografts with cyclosporin A.

Cyclosporin A (CyA), an investigational immunosuppressive drug, was tested for its ability as a single agent to prevent rejection and maintain function of islet cell tumors transplanted across a major histocompatibility barrier. Lewis rats have previously been shown by our group to reject the KX insulinoma in 7 to 10 days. CyA was administered to Lewis rats intraperitoneally for 21 days beginning 1 day before subcutaneous KX insulinoma engraftment. Dosage of 8 and 12 mg/kg/day failed to suppress rejection, as no palpable tumor or blood glucose level changes were observed. A dosage of 17 mg/kg/day allowed full allograft function without serious drug-related side effects in this short-term study. blood glucose levels in the successfully engrafted recipients fell to an average of 43 +/- 13 mg/dl. When CyA treatment was stopped, the insulinoma allografts were rejected within 14 days, suggesting that continued presence of the drug is necessary to maintain immunosuppression. These experimental results suggest that CyA can be administered as a single immunosuppressive agent to prevent early rejection of insulinoma transplanted across a major histocompatibility barrier in the experimental animal.

Adenoma, Islet Cell↗

PubMed1983

Functional and morphologic changes associated with insulinoma transplantation into diabetic rats.

Because of the technical difficulties encountered with human islet cell transplantation, alternatives toward supplying the juvenile diabetic with an endogenous insulin source are sought. With the use of a streptozotocin-induced diabetic rat model, it was found that by transplantation of a benign insulinoma, the glomerular deposition of material stained by the periodic acid-Schiff method, IgG, IgM, and C3 may be prevented. This effect was found only when transplantation of the insulin-producing tumor occurred within 2-4 weeks of the induction of diabetes. The data suggest that successful insulinoma engraftment can prevent the glomerular mesangial lesions from developing.

Adenoma, Islet Cell↗

PubMed1983

Comparison of monoamine oxidase in golden hamster islets and insulinoma.

We compared the properties of monoamine oxidase (MAO) in hamster islets and insulinomas. The tryptamine concentration at which the monoamine oxidase velocity was half maximal (Km) was higher in islets than insulinomas; the maximal velocity (Vmax) of monoamine oxidase was greater in islets than insulinomas. Both islet and insulinoma are more sensitive to inhibition by pargyline than clorgyline. After pargyline administration the monoamine oxidase activity of insulinoma returns faster than activity of islets. This may occur because both synthesis of new MAO in pre-existing cells and formation of new cells occurs in the insulinoma.

Adenoma, Islet Cell↗

PubMed1983

Lymphoscintigraphy for malignant melanoma. Surgical considerations.

Lymphoscintigraphy using technetium-99m atimony sulfur colloid was performed in 22 patients with melanoma referred to Duke University Comprehensive Cancer Center in an attempt to identify patterns of regional lymphatic drainage. Scans from six patients revealed lower extremity lesions with three located below the knee, one in the popliteal space, and two others proximal to the knee joint. Despite the location of the primary, all scans but one showed initial drainage to the inguinal nodes bypassing the popliteal lymph node group. Of the three patients who had primary melanoma of the posterior scalp, the lymphatic drainage was directed to the posterior cervical nodes. No drainage to the parotid nodes or anterior neck nodes was visualized. The knowledge gained from lymphoscintigraphy resulted in posterior neck dissections instead of the standard anterior neck dissection and superficial parotidectomy. In areas of ambiguous lymphatic drainage from the trunk, radiocolloid scanning can identify areas at risk for developing metastatic disease. Six lesions within 5 cm of the midline demonstrated bilateral axillary or groin drainage in 83 per cent of the patients. For two lesions near Sappey's line colloidal uptake to the ipsilateral axilla and groin was the rule. After a 3-year follow-up, during which time 70 to 90 per cent of lymph node metastases are predicted to occur, no nodal metastases were ever documented in areas that did not show colloidal uptake. No correlation was found between amount of radiolabel in positive compared to negative nodes, although those nodes that were completely replaced by tumor contained no 99mTc activity and were negative on scanning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

Metastatic malignant melanoma with an unknown primary.

Patients who are diagnosed initially as having metastatic melanoma with no known cutaneous, mucosal or ocular primary are a perplexing clinical problem. In the Duke University Melanoma Clinic, 124 patients have been identified as meeting the criteria of an unknown primary melanoma. This represents 4.8 per cent of the total melanoma population seen at this institution. There were 2.5 times as many males as females with an average age at diagnosis of 47.9 years. Regional lymph node disease was the most common presentation with 64 per cent of the patients falling into this category. Those patients who showed initial evidence of hematogenous spread of their melanoma had a worse prognosis than their counterparts who manifested primarily lymphatic spread. When compared with control population groups with known primary melanoma, the unknown primary group had equal survival emphasizing that surgical treatment should be similar for both groups.

Adolescent↗