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Biomedical subjects

R E Wilson

Publications and source records attributed to R E Wilson.

At least 91 records · Page 5Linked to original sources

Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy.

During a period of 7 years, we have aggressively treated liver tumors whether primary or metastatic. Our experience after 43 curative major liver resections has shown an excellent overall survival: 34 of 43 patients still alive a median of 12 months after liver resection (patient ages ranged from 21 to 85 years, median 57 years). Nineteen patients underwent right hepatic lobectomy, 9 trisegmentectomy, 5 left hepatic lobectomy, 5 extended left hepatic lobectomy, 4 right lobectomy plus left lobe wedge resection, and 1 patient underwent a major hilar wedge resection. Two patients died from sepsis and hepatic failure on or before the 60th postoperative day. One patient with no evidence of recurrent colorectal cancer was lost to follow-up after 2.5 years. One patient died without cancer 12 months after left hepatic lobectomy for colon cancer metastases. Cumulative survival for the entire series and for patients after resection of colorectal cancer metastases was the same: 1 year survival 90 percent; 2 year survival 75 percent, and 3 year survival 65 percent. Seventeen of 30 patients remain disease-free after resection of liver metastases. Of the 13 who had recurrence, 8 are still alive. Ten recurrences were outside of the residual liver (predominantly multiple pulmonary metastases). One recurrence was in the right hemidiaphragm, and only three were in the residual or regenerated liver. Serial carcinoembryonic antigen analysis was the best indicator of recurrence in these 13 patients, 12 of whom were asymptomatic. These data confirm that major liver resection can be performed with minimum postoperative mortality (4.7 percent in this series). More importantly, the majority of patients were cured of their liver metastases. The next goal should be the initiation of adjuvant systemic therapy trials after liver resection in such patients.

Adult↗

The relationship of body temperatures to the efficacy of chemotherapy against systemic metastases from B16 melanoma.

Potential synergy between physiologic levels of heat and chemotherapy was investigated in C57BL/6 mice bearing the B16 melanoma. Low levels of hyperthermia alone had no effect on the growth of the primary tumor but augmented the growth delay induced by cyclophosphamide. Although the addition of hyperthermia to chemotherapy and amputation increased the duration of survival and decreased the number of pulmonary metastases, heat did not increase the cure rate of animals with gross or microscopic pulmonary metastases. The incidence of local recurrence was decreased by hyperthermia in animals treated with chemotherapy and incomplete excision of the primary tumor.

Animals↗

Current treatment of metastatic renal cell carcinoma with xenogeneic immune ribonucleic acid.

In 1979 we reported a phase I trial involving 6 patients treated with immune ribonucleic acid for renal cell carcinoma. Since that report 27 patients with stage III or IV renal cell carcinoma have been assessed in a phase II trial. All patients have undergone excision of the primary tumor or superficial metastases, injection of tumor into guinea pigs and harvesting of immune ribonucleic acid. Autologous lymphocytes, obtained by plasmapheresis on an outpatient basis, have been incubated with immune ribonucleic acid and reinfused into the host. Results indicate complete response in 1 patient for more than 61 months, partial response in 5 patients for 6 to 10 months and stabilization in 10 patients for 2 to 8 months, all of whom had progressive disease before the institution of therapy. Six patients with continued progressive disease died at a median of 2 months after therapy. Of 5 patients treated in an adjuvant fashion only 1 has had a relapse from 9 to 18 months after therapy. Patients with pulmonary metastases seem to represent the most favorable group for this passive form of immunotherapy. This therapy would seem to offer reasonable alternatives in selected patients with advanced disease.

Adenocarcinoma↗

Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis.

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.

Animals↗

Intraductal carcinoma of the breast.

The management of intraductal carcinoma of the breast at the present time is necessarily diverse because there is difficulty in detecting it, as well as understanding its basic biology and natural history. Therapy has ranged from excisional biopsy with or without radiation to radical and extended radical mastectomy. The effects of radiation therapy upon these well-differentiated in situ lesions is undefined. The popularity of total mastectomy stems from a concern for the fate of breast tissue left in situ after removal of the focus of preinvasive carcinoma. Intraductal carcinoma of the breast has been shown to be a multicentric disease process in a large percentage of patients. Indeed, all breast tissue in these patients appears to be at risk for the eventual development of preinvasive and invasive carcinoma. However, the clinical significance of such residual foci of in situ carcinoma or ductal hyperplasia and dysplasia following resection of the breast, as in papillary carcinoma of the thyroid, is still open to question. Similar concern exists for a significant "sampling error" involved in biopsies of lesions of the breast: there were six instances of this in the present series (11 per cent). A "sampling error" of 6 per cent was found in a similar study of a group of patients with intraductal carcinoma. An error rate of 18 per cent was reported in another study. Again, the clinical significance of this "sampling error" remains open to question. The difficulty encountered in evaluating remaining breast tissue after a partial mastectomy has also been reason to consider total mastectomy in these patients. Residual or recurrent carcinoma in such altered breast tissue is difficult to diagnose at an early stage, either by physical examination or by the results of mammography. None of the patients in the present series had axillary nodal metastases and, theoretically, intraductal carcinoma should not be associated with axillary nodal metastasis. The small percentage of patients found to have invasive carcinoma following mastectomy for in situ carcinoma are likely to have minimally invasive lesions with, at most, a 23 per cent incidence of positive axillary nodes. The advantage gained by performing full axillary dissection or extensive nodal sampling in 60 per cent of the patients in this series, as well as in patients in other series, is difficult to ascertain without further study. The most logical choice of therapy would appear to be total mastectomy with limited axillary node sampling.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia.

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.

Antigen-Antibody Complex↗

Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.

With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.

1-Butanol↗

The 1982 national survey of carcinoma of the breast in the United States by the American College of Surgeons.

The 1982 survey documented changes in the management of carcinoma of the breast in this country. If one compares the current survey results with the results of the 1978 survey, an inescapable conclusion is that there is a changing understanding of carcinoma of the breast and a willingness to apply new knowledge to clinical practice. These results also show the potential of the hospital Tumor Registry when records are systematically aggregated and data from different points compared. Future applications of this survey procedure and further analyses of these data may be used to document progress in the control of cancer. While useful for these purposes, it should be noted that these data are not intended, nor suited, for assessing the superiority of given treatments. They may not reflect the outcome that would result from a clinical trial. Comparisons made herein often involve patients who differed in many respects other than that on which the comparison was focused. However, within these constraints, the data may be useful for clinicians and scientists interested in the dynamic state of the treatment of carcinoma of the breast in large numbers of hospitals in the United States.

Adult↗

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.

1,2-Dimethylhydrazine↗

Survival of patients with localized high-grade soft tissue sarcoma with multimodality therapy. A matched control study.

Ten of 16 consecutive patients (63%) with Stages III-IVA soft tissue sarcoma presenting between 1975 and 1978 and treated with surgery, radiotherapy and adjuvant chemotherapy have remained disease-free with a median follow-up of three years (range, 28-68 months). Survival at three years was 86%. However, in the American Joint Committee (AJC) soft tissue sarcoma staging system published in 1977, Grade 3 soft tissue sarcomas were associated with a three-year survival of 35% and almost 90% of the patients destined to fail did so within three years of diagnosis (8). To determine if the observed improvement in survival resulted merely from lesions with favorable prognostic determinants at diagnosis, study patients were matched for stage, histologic type and location of the primary lesion with controls generated from these 1215 carefully reviewed sarcoma patients collected from the data base of the Task Force on Soft Tissue Sarcomas of the AJC. Only control cases whose histology had been reviewed and who had been treated with surgery (with or without radiotherapy) were included in the analysis. Cases survived significantly longer than controls at three years (p less than 0.001) and, in fact, disease-free survival of cases (63%) was superior to overall survival of controls (27%) (p less than 0.01). Our data support the conclusion that patients with high-grade soft tissue sarcoma treated by an experienced multimodality team have a three-year disease-free survival of approximately 63%. The impact of each component of multimodality therapy cannot be determined, and improved survival may result, in addition, from improved diagnostic and staging techniques currently available.

Adult↗

Gut-associated lymphoid tissue and dimethylhydrazine-induced colorectal carcinoma in the Wistar/Furth rat.

Although gut-associated lymphoid tissue in the form of discrete lymphoid patches (LP-GALT) in mammalian intestine in most prominent in the distal ileum, appendix, and, in some species, the cecal appendage, LP-GALT can be found throughout the intestinal tract. LP-GALT appears as single or multiple subepithelial lymphoid follicles covered by a specialized, structurally unique epithelium. In the colon of the Wistar/Furth (W/Fu) rat, LP-GALT appears as aggregates of follicles, or lymphoid patches, that can be detected macroscopically. We studied the relationship between 1,2-dimethylhydrazine- (DMH) induced colon carcinomas and the lymphoid patch associated epithelium in these animals. In addition, we defined the normal distribution of colonic lymphoid patches in both DMH-treated and control rats. Patches were found macroscopically and confirmed by histologic examination at five constant sites: lower pole of cecum, proximal ascending colon, the major colonic flexure, mid descending colon, and the rectosigmoid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be detected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be associated with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found associated with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium.

Animals↗

Interaction of Ia antigen-bearing polymorphonuclear leukocytes and murine splenocytes.

Polymorphonuclear leukocytes (PMN) were induced in the peritoneum of a Balb/c mouse by ip injection of Fusobacterium nucleatum (FN) (greater than 95% PMN). A subpopulation of PMN harvested bore Ia surface antigens and stimulated a mixed lymphocyte reaction (MLR) when cultured with C57B1/6J splenocytes. The reaction was blocked by a short prior incubation of PMN with anti-Ia antibody or PMN cell depletion by the same antibody plus complement. The Ia antigen-bearing PMN were capable of antigenic modulation since incubation of PMN for 24 h rendered the cells incapable of stimulating an MLR. The Ia antigen-bearing PMN produced a soluble material that enhanced the phytohemagglutinin (PHA) response of murine splenocytes and the active material was a product of live cells since the supernatants contained no detectable lactate dehydrogenase activity. The data suggest that murine PMN subpopulations, defined by surface Ia antigen, can modulate mitogenic responses by production of an enhancing factor(s).

Animals↗

Nuclear magnetic resonance for the differentiation of benign and malignant breast tissues and axillary lymph nodes.

We have utilized proton T1 (spin-lattice relaxation time) values of Nuclear Magnetic Resonance to study 110 tissue samples obtained from 11 mastectomy specimens. Samples of 1 cm3 from primary tumor sites, nipples, and other breast quadrants, as well as intact lymph nodes were studied and then histologically scored for the presence or absence of carcinoma and, if present, whether it was an isolated microscopic focus (micro). Of 54 samples of breast tissue, 12 contained carcinoma, 5 micro: of 45 lymph nodes, 15 contained metastatic carcinoma, 2 micro; of the 11 nipples, 2 had carcinoma, both micro. For the malignant samples (excluding micro) mean T1 value was 0.47 +/- 0.07 sec, (range 0.39-0.79 sec). For the 72 benign samples (excluding nipple) mean T1 value was 0.26 +/- 0.03 sec (range 0.14-0.36 sec). The 13 tumor-bearing nodes had a mean T1 value of 0.47 +/- 0.03 sec (range 0.40-0.63 sec); mean for the benign nodes was 0.26 +/- 0.007 sec (range 0.19-0.35 sec). The differences were highly significant in each case (p less than 0.001). For micro examples, T1 values were at malignancy threshold levels or just below, except for nipple tissues, where discrimination was poor. For the 20 other malignant samples, there was no correlation between T1 value and the per cent of sample containing malignancy.

Axilla↗

Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.

Adult↗