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Biomedical subjects

H F Seigler

Publications and source records attributed to H F Seigler.

At least 109 records · Page 6Linked to original sources
PubMed1988

Stage II malignant melanoma: presentation of a prognostic model and an assessment of specific active immunotherapy in 1,273 patients.

The ability to redefine risk factors and to predict prognosis in patients with malignant melanoma at the time they manifest nodal metastasis can be a benefit to the patient emotionally and to the physician therapeutically. A retrospective review of 1,273 patients with stage II malignant melanoma was performed at our institution. The most significant prognostic factors in a simultaneous hazard Cox multivariate analysis, predicting melanoma-related mortality among stage II patients, were the number of positive nodes (P less than 0.0001), age (P = 0.0004), site of the primary lesion (P = 0.0036), disease-free interval (P = 0.016), thickness of the primary lesion (P = 0.017), and sex of the patient (P = 0.0616). We have developed a model for predicting survival of stage II patients, designed for use in the clinic setting. Its application in a computer system makes it accessible and understandable. The most favorable risk group (18% of the population) has actuarial 5- and 10-year survival rates of 58% and 49%, respectively, from the time of the nodal metastasis. The least favorable risk group (7% of the population) has 5- and 10-year survival rates of 15% and 10%, respectively. There are three intermediate risk groups. All groups differ prognostically (P less than 0.04). The principal adjuvant therapy offered to these patients was specific active immunotherapy, which appears to have a 10-20% survival benefit in stage II patients with greater than one positive node, when compared with institutional controls. The apparent survival benefit of the immunotherapy supports continued clinical investigation of its therapeutic potential.

Actuarial Analysis↗
PubMed1988

Lethal "thin" malignant melanoma. Identifying patients at risk.

Thin melanomas can metastasize and be lethal. The purpose of this review was to identify negative risk factors in patients with melanomas less than 0.76 mm thick. Six hundred and eighty-one (681) such patients are reviewed in this study. Of those referred without metastatic disease (583 patients), metastases developed in 4.8% after a mean followup of 3.6 years. Of those referred with metastatic disease (98 patients), mortality was 35% after a mean followup of 5.9 years. Male patients (p less than 0.04) and patients with axial primaries (p less than 0.05) were at an increased risk of metastasis. Severe histologic regression was present in 40% of the primary lesions that metastasized and in only 17% of similar lesions that did not (p less than 0.001). Increased age was associated with increased local skin metastases, but not with increased nodal or distant metastases. A prognostic model was designed, using two clinical risk factors (axial primary site and male sex) and two histologic risk factors (Clark's Level IV and severe histologic regression). The prognostic model identified a low-risk population--women with extremity primaries--with an actuarial risk of metastasis at 10 years that was less than 3%. Patients with either (1) both clinical risk factors or (2) one clinical risk factor and one histologic risk factor were identified as high-risk patients. Their actuarial risk of metastasis was 11% at 5 years and 22% at 10 years (p = 0.0084). Identifying high-risk and low-risk patients with thin melanomas may improve guidelines for the application of adjuvant therapies to this population.

Adult↗
PubMed1988

DU-PAN-2 levels in serum and pancreatic ductal fluids of patients with benign and malignant pancreatic disease.

Previous studies have shown that the DU-PAN-2 antigen is elevated in approximately 70% of serum samples obtained from pancreatic adenocarcinoma patients, and within the normal range (less than 400 U/ml) in 99% of normal subjects. In this study, the DU-PAN-2 antigen level of the serum and pancreatic ductal fluid in patients with malignant pancreatic disease were compared to antigen levels in patients with benign pancreatic diseases. Six percent of patients with chronic pancreatitis and 13% of patients with severe acute pancreatitis had elevated DU-PAN-2 antigen levels in their sera. Pancreatic ductal fluid DU-PAN-2 levels were elevated in 33% (11 of 33) of patients with pancreatic adenocarcinomas, whereas 16% (5 of 31) of patients with chronic pancreatitis and 38% (8 of 21) of control patients had elevated secretion levels. Unlike DU-PAN-2, the tumor markers carcinoembryonic antigen (CEA) and carcinoma (CA) 19-9 were elevated in 90 and 100%, respectively, of secretions of patients with pancreatic adenocarcinoma. However, CEA and CA 19-9 ductal fluid levels were also elevated in patients with chronic pancreatitis (CEA: 61%; CA 19-9: 85%), and therefore these markers are not helpful in distinguishing benign from malignant pancreatic disease. The physiologic implications of elevated DU-PAN-2 serum antigen levels in patients with normal ductal fluid DU-PAN-2 levels are discussed.

Adenocarcinoma↗
PubMed1988

Juvenile malignant melanoma of the head and neck.

Malignant melanoma of the head and neck is a potentially lethal disease and considered rare among juveniles. Treatment patterns have historically been dictated by experience with adults, however a paucity of data is available to determine the natural history and treatment guidelines for juveniles and children with malignant melanoma. Therefore a retrospective computer-aided analysis of patients less than 20 years of age having malignant melanoma were obtained from the records of 4,843 patients with malignant melanoma recorded from 1972 through 1986. Eighty-seven patients were identified from this group with 17 patients having primary malignant melanomas confined to the head and neck. Parameters evaluated were age at diagnosis, sex, type of melanoma, Clark Level, Breslow depth of invasion, pathologic classification, site of primary, nodal status at diagnosis, surgical treatment, recurrence rate and site of recurrence, and follow-up status. Two of 17 patients had stage II disease and were treated with wide local excision and therapeutic radical neck dissection. Fifteen of 17 patients initially presented with stage I disease were treated with wide local excision. Two of these patients underwent elective radical neck dissection both of which proved to have positive occult nodal disease. Both are alive without evidence of disease 2 1/2 to 7 years later. Of the 13 patients who were initially treated with only wide local excision, nine patients developed local (3), regional (3), or systemic (3) disease within 3 months to 9 years from the date of diagnosis. Seven of the nine died of their disease 5 months to 20 years later. When juvenile patients with melanomas of the head and neck are compared to a comparable age group of patients with melanomas at other primary body sites, the head and neck group had a significantly higher frequency of death. Compared to the adult head and neck population, juvenile patients had identical actuarial survival time, but shorter disease-free intervals, even though the adult population had a higher percent of poor prognostic indices (presence of ulceration and thickness of lesions). Failure to control local and regional disease coupled with the overall poor survival rate, indicates that malignant melanoma occurs in the young as a biologically active tumor and suggests an aggressive approach for better control of local and regional disease and, hopefully, survival.

Adolescent↗
PubMed1987

Inflammatory breast carcinoma. Effective multimodal approach.

Twenty-two patients with inflammatory breast carcinoma received preoperative chemotherapy consisting of weekly administration of cyclophosphamide, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate for six weeks. Postoperative therapy consisted of 22 weeks of biweekly administration of these drugs. Regional radiotherapeutic consolidation followed chemotherapy. Nineteen patients completed therapy. Twelve of these patients remain disease free (median, 15 months; range, four to 32 months). Median disease-free survival for all 22 patients is 13 months or more (range, zero to 32 months). Median overall survival is 18 months or more (range, one to 33 months). This regimen compares favorably with prolonged adjuvant and maintenance chemotherapy for inflammatory breast carcinoma.

Adult↗
PubMed1987

Prognosis for recurrent stage I malignant melanoma.

The outcome of patients with stage I malignant melanoma has been well assessed in terms of prognostic factors and their effect on survival; however, little is known of the recurrence patterns of cutaneous melanoma or the survival of these patients subsequent to recurrence. A retrospective, computer-aided chart review identified 4185 patients with melanoma who had stage I disease clinically. During a follow-up period of one to 14 years, 35.9% suffered a recurrence. Melanoma of the trunk (37.8%) and head and neck area (46.1%) had an increased incidence of recurrent metastases compared with melanoma of the extremities (29.8%). Local regional metastases accounted for 62.5%, 77.3%, and 85.6% of the recurrences in the head and neck, trunk, and extremity primary sites, respectively, with 65% of the relapses occurring within the first three years. Actuarial five-year survival rates of patients who had recurrent disease were significantly decreased compared with those of patients who had no evidence of metastases during their clinical course. A multivariate analysis was performed to estimate the survival of patients after recurrence. One may use this mathematical model to predict the outcome of individual patients after recurrence and provide a more rationally based prognosis for them and their families.

Adult↗
PubMed1987

Human T cells specifically activated against autologous malignant melanoma.

Lymphocytes from ten patients with melanoma were specifically stimulated in vitro with autologous melanoma cells and expanded in interleukin 2. Significant lysis of autologous melanoma cells was demonstrated in T cells derived from six of these patients. The mean percent of lysis of autologous tumor cells at an effector-target ratio of 20:1 was 46% among these six patients. The T cells derived from two patients developed specificity in lysing autologous melanoma cells. In both cases, specificity was enhanced by the in vitro stimulation with autologous tumor cells. Restimulation with autologous melanoma cells was associated with increasing specificity over time. Whether derived from peripheral blood lymphocytes or from lymph node cells, T cells from one patient lysed fresh autologous melanoma cells more potently than K562, allogeneic melanoma cells, and nonmelanoma cells. On day 38, at an effector-target ratio of 10:1, cell lysis of K562, an osteosarcoma, a pancreatic cancer, and three allogeneic melanomas was 3%, 4%, 7%, 8%, 7%, and 2%, respectively, while lysis of autologous melanoma cells was 47%. Specificity was maintained beyond day 60. The T cells could be expanded over 50-fold within one month.

Cell Separation↗
PubMed1987

Immune response of chimpanzee to purified melanoma 250 kilodalton tumor-associated antigen.

Melanoma high molecular weight tumor-associated antigen (TAA), having a molecular weight of 250 kilodaltons (Kd), was purified from a crude cell membrane extract through a combination of lectin affinity, immunoadsorption, and high performance liquid molecular filtration chromatography. Compared to the starting extract, purified TAA was 600-fold higher in TAA activity per microgram of protein. Purified TAA was used to immunize a chimpanzee and the resulting antiTAA immune response was evaluated. Postimmune chimpanzee serum reacted in solid phase radioimmunoassay against purified TAA with a titer in excess of 100,000. In contrast, preimmune serum had a titer of less than 100 in the same assay. By immunoprecipitation analysis, we were able to demonstrate reactivity of the chimpanzee immune serum with a 250 Kd TAA in spent culture medium from melanoma cells metabolically labeled with 35S-methionine and with iodinated purified 250 Kd TAA. Reactivity of the chimpanzee antiserum for the 250 Kd TAA was confirmed in blocking and reciprocal immunodepletion studies using murine monoclonal antibody 9.2.27. These studies suggest that the 250 Kd TAA defined by murine monoclonal antibodies may prove to be immunogenic in man and that manipulation of the immune response to this TAA might be used to the clinical benefit of the patient.

Animals↗
PubMed1987

The prognostic significance of recall antigen testing in melanoma patients.

A quantitative assessment of the long-term prognostic value and clinical usefulness of recall antigen reactions in patients with malignant melanoma is not available. The authors evaluated longitudinal observations of survival made in 846 patients over a 12-year period. Each patient was initially studied with Mantoux-type recall antigen skin tests. The patients were categorized with respect to the following: high (greater than 5 mm) or low (less than or equal to 5 mm) averaged skin test reaction diameters at 48 hr; Clark level; tumor stage (I = localized tumor, II = local extension and/or region lymph node metastasis, III = systemic metastasis); ulceration; site of primary; histologic type; age; and sex. The percentage of high reactors in Stages I, II, and III were 44.3%, 37.4%, and 25%, respectively. Survival was evaluated with the Cox-Mantell hazard function model and the Cox regression model. The significant (chi-squared; probability) risk factors detected were tumor stage (94.58; less than or equal to 0.0001), Clark level (19.37; less than or equal to 0.0001), sex (16.97; less than or equal to 0.0001), and skin test reactivity (7.48; less than or equal to 0.0062). A significant relationship also was detected between skin test reactor status and the tumor stage (p less than or equal to 0.0330). When evaluated within each stage of disease, skin test reactivity predicted survival only in Stage II patients (p less than or equal to 0.0080). Five-year survival estimates among Stage II patients were 58% among high reactors and 38% among low reactors.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Early results with combined modality therapy for carcinoma of the esophagus.

Since January 1984, 74 patients (61 men, 13 women; age range: 43-76 years) with carcinoma of the esophagus were evaluated. Fifty-two patients had squamous cell carcinoma and 22 patients had adenocarcinoma. Sixty-three patients had preoperative chemotherapy and radiation that consisted of cis-platinum and VP-16 for squamous cell carcinoma and cis-platinum 5-FU for adenocarcinoma combined with 4500-6000 rads. Thirty-four patients were staged inoperable at the completion of the 4-month treatment regimen. Eleven patients had surgery alone because they refused or were not candidates for the preoperative regimen. Twenty-nine patients completed the combined modality regimen and have had esophagogastrostomy. All patients receiving chemotherapy and radiation demonstrated improved swallowing and a dramatic reduction of tumor mass early in the course of therapy and have been able to maintain oral nutrition without other support in the posttreatment period. Of the 34 patients who had chemotherapy and radiation therapy as palliation, 18 are currently living. One patient died secondary to complications of chemotherapy, another patient died at 9 months of myocardial infarction. The remaining patients died secondary to their disease. Of the 29 patients who had radiation therapy and chemotherapy plus esophagogastrostomy, 25 are alive. There were no operative deaths. One patient died at 9 months of stroke. Three other patients had recurrence and died 1 year after surgery. Of the 11 patients who had surgery alone, two have died of the disease. Of the 29 patients who completed the integrated therapy, 10 had no evidence of residual tumor in the specimen, and in an additional five patients only microscopic foci were evident. These early results are an encouragement to continue the multidiscipline approach to carcinoma of the esophagus in the hope that the quality of life and disease-free interval, as well as ultimate survival, will be enhanced.

Adenocarcinoma↗
PubMed1987

Absence of estrogen receptor in human melanoma as evaluated by a monoclonal antiestrogen receptor antibody.

Controversy regarding the presence of estrogen receptor proteins in human melanomas persists despite extensive investigations on this subject. While apparent high-affinity binding has been observed using dextran-coated charcoal assays, several other characteristics of receptor protein have not been observed. The production of free water on incubation of tritiated estradiol (labeled in the C2 position) with melanoma cytosols suggests the possibility that the apparent binding observed is due to phenomena other than specific receptor-steroid interactions. Melanomas from 15 patients were evaluated for the presence of estrogen receptor using immunocytochemical techniques with a monoclonal antibody directed against the human estrogen receptor protein (H222 Sp gamma). Immunohistochemical evaluation included intensity and distribution of staining. None of the 15 cases demonstrated specific immunohistologic reactivity with the anti-receptor antibody. Control breast and uterine tissue confirmed the specificity and sensitivity of the methods. These results suggest that the apparent estrogen-binding capacity of human melanoma tissues is the result of interactions other than with estrogen receptor, and reaffirm the need to investigate alternate steroid protein interactions, such as catechol estrogen formation, in studying sex steroid influences on human melanoma.

Adult↗
PubMed1986

Investigative studies in the diagnosis and treatment of melanoma.

Patients with melanoma have prognostic indicators that can be accurately assessed using standard histopathologic techniques. First-order lymph node disease plays a significant role in determining both the prognosis of the patient and the therapeutic benefit in selected patients. The lymph nodes at risk can be determined by the technique of lymphoscintigraphy, and specificity might be possible using isotopically labeled monoclonal antibodies. Techniques utilizing immunohistology and immunocytology have been developed and applied to the clinical setting. Early diagnosis of recurrent disease is now possible using radioimmunoassays. Specific immunotherapy trials are underway and early results are encouraging.

Antibodies, Monoclonal↗
PubMed1986

Diagnosis of metastatic malignant melanoma by fine needle aspiration biopsy: a clinical and pathologic correlation of 298 cases.

Fine needle aspiration biopsies (FNABs) from 298 lesions in patients with suspected metastatic melanoma were studied. The results were correlated either with histopathologic diagnoses on resected lesions or with prolonged clinical follow-up. Of 165 malignant aspirates, 160 were confirmed either by surgical resection (65 cases) or by an appropriate clinical course (95 cases). Of the 107 benign lesions with adequate follow-up, 73 were confirmed as benign. There were 25 false negatives: 19 were inadequate samples, and 6 were presumed failures of needle localization. No interpretative errors were identified. Although 3 cases of FNAB-diagnosed malignant melanoma could not be confirmed by surgical biopsy, the cytologic findings were typical of malignant melanoma. Clinical follow-up, however, suggested that the cytologic diagnosis was in error. One case of a second unrelated malignancy (an adenocarcinoma of the lung) was correctly diagnosed with the use of FNAB. Because of its high degree of accuracy, FNAB has proved useful in the differential diagnosis of subcutaneous nodules, enlarged lymph nodes, and lung nodules.

Biopsy, Needle↗
PubMed1986

Pectoralis pyomyositis: an unusual cause of chest wall pain in a patient with diabetes mellitus and rheumatoid arthritis.

We describe a case of isolated pectoralis swelling and tenderness, without systemic signs of infection, in a North American adult with diabetes mellitus and rheumatoid arthritis. The etiology was discovered to be pyomyositis, usually thought to be a disease of tropical climates. It is the first such case with group B Streptococcus as the causative organism.

Arthritis, Rheumatoid↗
PubMed1985

Malignant melanoma and pregnancy.

Confusion exists concerning the influence of pregnancy on survival in patients with malignant melanoma. To evaluate this problem a retrospective computer-aided study was performed of women in the child-bearing years treated for Stage I cutaneous melanoma at the Duke University Comprehensive Cancer Center. Fifty-eight women were identified who had melanoma arise during pregnancy (Group 1) and 43 patients were noted who became pregnant within 5 years of diagnosis of their melanoma (Group 2). Appropriate control groups matched for the clinical variables of age, primary site, and stage of disease and the pathologic variables of Clark's Level, tumor thickness, ulceration, and histologic type were selected from the cohort of 2938 melanoma patients seen at Duke. Actuarial survivals for Group 1 and 2 patients did not differ from their respective controls, although the small number of deaths in each group resulted in wide confidence intervals. When actuarial disease-free intervals were plotted, there was a significant difference between women who had melanoma develop during pregnancy when compared to their controls (P = 0.04). In a multivariate regression analysis, after adjustment for the influence of the more significant prognostic factors for Stage 1 melanoma, including Clark's Level, ulceration and tumor thickness, the effect of pregnancy on disease-free interval became more apparent (P = 0.02). No difference in actuarial disease-free interval was noted in the melanoma patients who elected to become pregnant within 5 years of diagnosis (P = 0.31). A multivariate regression analysis confirmed this finding. These data indicate that although an intercurrent melanoma during pregnancy has a worse prognosis than the control groups, once a woman has been diagnosed as having a cutaneous melanoma, a subsequent pregnancy has no effect on recurrence rate or survival.

Actuarial Analysis↗
PubMed1985

Pharyngoesophageal reconstruction using free jejunal interposition grafts.

Forty patients underwent pharyngoesophageal reconstruction with a free jejunal interposition graft (FJIG). Three categories of disease were treated: (1) primary upper aerodigestive tract carcinomas, (2) recurrent carcinomas, and (3) benign pharyngoesophageal stenosis. There were no intraoperative graft failures. Postoperative complications included four perioperative deaths, eight late graft failures, three transient fistulas, eight distal graft strictures, one prolonged ileus, two postoperative hematomas, one abdominal wound dehiscence, one abdominal abscess, and one hypoglossal nerve palsy. Of the eight patients with late graft failures, three underwent successful jejunal reimplantation, yielding an overall success rate of 88% (35/40). The advantages of an FJIG are as follows: (1) a single-stage procedure for large defects, (2) a jejunal segment approximately the size of the pharyngoesophagus, (3) tissue that is able to tolerate radiation therapy, (4) maintenance of near-physiologic swallowing mechanism, (5) denervated small-bowel model, (6) excellent palliative procedure, and (7) shortened hospitalization. Disadvantages include (1) microvascular surgical technique, (2) abdominal procedure, and (3) limited esophageal speech.

Adult↗
PubMed1985

Immunodiagnosis of human malignancy.

Definition of normal cell membrane antigens using immunologic techniques has permitted investigators to distinguish normal cells from malignant cells. Malignant cells express fetal antigens in concentrations different from normal mature cells. Mutant cells express differentiation as well as those antigens reflecting the altered cell genome. Normal cells can be transformed into malignant cells using either chemical agents or viruses. As these agents are incorporated into the genome, surface antigens are expressed that differ from normal cell isoantigens. These antigenic determinants can serve as tumor-associated or perhaps tumor-specific markers. Immunochemical methods now exist that permit isolation and purification of these antigens. Monoclonal antibodies have been generated that react with single epitopes associated with these antigens. Very sensitive and highly specific radioimmunoassays and enzyme immunosorbent assays can detect microgram quantities of these antigens in body fluids and as such permit serodiagnostic evaluation. Monoclonal antibodies can also be used for radioautography, immunofluorescent, and immunoperoxidase staining for diagnostic purposes of both cytologic and fixed tissue sections. The binding affinity and specificity of these monoclonal antibody reagents has successfully been used for in vivo tumor localization. Isotopically labeled monoclonal antibodies bind preferentially to tumor cells in the host and are useful for specific radionuclide scintigraphy. These recently developed immunodiagnostic techniques not only add specificity in terms of diagnostic accuracy but are useful for early detection of recurrent disease and in vivo localization of tumor deposits. Therapeutic implications are discussed.

Antibodies, Monoclonal↗