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Biomedical subjects

R E Wilson

Publications and source records attributed to R E Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Abdominal pain in neutropenic cancer patients.

A review of 58 patients with malignancies (age range, 14-73 years), who required surgical consultation for acute abdominal pain in the setting of neutropenia (granulocyte count less than 1000/mm3) after chemotherapy was conducted. Ninety percent had fevers greater than 37.8 degrees C, 30% had diarrhea or melena, and 25% had diminished bowel sounds. Five of the 29 patients (17%) with localized pain had surgical intervention; 3 of 29 patients (10%) with generalized pain underwent operations (2 for x-ray findings). All eight of these surgically treated patients survived to leave the hospital. Eighteen of the 29 patients with generalized pain were believed to have a similar syndrome of diarrhea (occasionally heme positive) and diffuse abdominal tenderness (some with peritoneal signs and distension), which was termed "neutropenic enteropathy." Eleven of these 18 patients had their symptoms resolve with antibiotic therapy, aggressive fluid replacement, and a return of their granulocyte count to normal. The other seven died of pneumonia (two), unknown causes (one), and diffuse enterocolitis throughout the intestinal tract (four documented at autopsy). The overall 30-day mortality rate in this series was 34%. Several factors correlated significantly with mortality: hypotension at the onset of pain (80% mortality), bacteremia (63% mortality), and fungemia (100% mortality). Absolute leukocyte count and absolute platelet count did not correlate with mortality. This study reaffirms that patients with neutropenic enteropathy are best treated conservatively. Patients with surgically correctable disease were identified by specific focal findings on examination or x-ray.

Abdomen↗
PubMed1986

Inhibition of rat colon tumor isograft growth with dequalinium chloride.

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma.

Animals↗
PubMed1986

Doxorubicin chemotherapy in the treatment of soft-tissue sarcoma. Combined results of two randomized trials.

In 1978, there were initiated two independent randomized, prospective trials of adjuvant doxorubicin hydrochloride (Adriamycin) following primary therapy for soft-tissue sarcoma. The virtual identity of these two protocols permits their combination for analysis. A total of 75 patients (42 men, 33 women) with soft-tissue sarcoma (stages IIB to IVA) were randomized, after receiving optimal regional therapy, to receive either doxorubicin hydrochloride (450 mg/m2) (37 patients) or observation (38 patients). Follow-up has ranged from 16 to 80 months (median, 49 months). Twenty-five patients (33%) died, and two patients receiving doxorubicin developed cardiotoxicity. No significant differences in local control, metastasis-free survival, disease-free survival, and overall survival were observed for the two treatment arms. Despite temporary prolongation of disease-free survival with doxorubicin in some subgroups, we conclude that there is no advantage to the use of adjuvant doxorubicin in the treatment of soft-tissue sarcoma.

Clinical Trials as Topic↗
PubMed1986

Surgical oncology in university departments of surgery in the United States.

Data on surgical oncology and multidisciplinary cancer program activity were obtained from 124 of 126 university surgery departments in the United States. Most of these institutions have American College of Surgeons-approved cancer programs (84%) as well as divisions of medical (95%), radiation (94%), pediatric (76%), and gynecologic (79%) oncology. Only 47 departments (38%) have formal divisions of surgical oncology. There are no major staffing or activity differences in surgical departments with or without such divisions, but multidisciplinary cancer program activity is greater in those institutions with a surgical oncology focus. Peer-reviewed cancer research grants are more frequent in departments of surgery with a surgical oncology division (68% vs 47%). The activities of the existing 47 divisions of surgical oncology are mainly operative, with breast cancer, melanoma, and soft-tissue sarcomas being the major clinical responsibilities. Chemotherapy is also frequent (81%). Cancer education for undergraduate and postgraduate surgical trainees is a major responsibility of most divisions, but only a small proportion (28%) have postresidency surgical oncology training programs. In contrast to the growth of some oncologic specialties, the establishment of surgical oncology within university departments has been slow, and the manpower needs appear modest.

Academic Medical Centers↗
PubMed1986

Local recurrence and the deep resection margin in carcinoma of the breast.

Deep resection margin of carcinoma of the breast is an important determinant of the extent of surgical resection as well as the use of adjunctive therapy. To investigate the relationship between deep resection margin and local recurrence, we retrospectively reviewed 105 consecutive female patients with clinical or pathologic Stage II infiltrating ductal carcinoma of the breast. All patients underwent a modified radical mastectomy with the removal of an intact pectoral fascia. The deep margin of resection was determined by histopathologic examination. Detailed follow-up information was obtained for 100 patients. In this study group, the distance from the tumor margin to the pectoral fascia did not correlate with local recurrence. Seventy-seven patients had deep margins of 1 centimeter or less; eight patients had a local recurrence. Recurrence in this group did not correlate with the distance from the deep margin (p = 0.92). The adjunctive administration of radiation therapy or chemotherapy did not appear to influence the frequency of local recurrences. These data suggest a deep margin consisting of an intact pectoral fascia may be adequate to prevent local recurrence in patients with infiltrating carcinoma of the breast.

Breast Neoplasms↗
PubMed1985

Mutagenicity tests of lipid oxidation products in Salmonella typhimurium: monohydroperoxides and secondary oxidation products of methyl linoleate and methyl linolenate.

Nine hydroperoxy and hydroperoxy-epidioxy oxidation products derived from either autoxidation (AO) or photosensitized oxidation (PO) of methyl linoleate (MLo) or methyl linolenate (MLn) were tested for mutagenic activity by the Salmonella typhimurium his+ reversion assay using strains TA100, TA98, TA102, TA97 and TA1537. All nine oxidation products, monohydroperoxides from AO-MLn (I) or from PO-MLn (II), dihydroperoxides from PO-MLo (III), AO-MLn (IV) or PO-MLn (V), hydroperoxy epidioxides from PO-MLo (VI), AO-MLn (VII) or PO-MLn (VIII) and hydroperoxy bis-epidioxides from PO-MLn (IX), were weakly mutagenic in strains TA97 and/or TA100. The hydroperoxy epidioxides (VI-IX) exhibited significantly greater activity in strain TA97 than did the monohydroperoxides (I, II) or the dihydroperoxides (III-V). In strain TA100, all of the oxidation products tested exhibited similar activity. No major differences between products derived from autoxidized and photooxidized MLn (I v. II, IV v. V, VII v. VIII) were obtained. Rat-liver S-9 reduced the toxicity of all oxidation products to the tester strains. The greatest mutant yields were usually obtained in the presence of S-9, but mutagenic potency was sometimes greater without S-9. The structural feature common to all of the mutagenic oxidation products was the presence of a hydroperoxy group, suggesting that this characteristic is responsible for the observed mutagenicity, either directly or through a common degradative pathway to reactive products of lower molecular weight.

Animals↗
PubMed1985

Colorectal carcinoma in patients under age 40.

Patients under the age of 40 with colorectal cancer (29 females, 18 males) were compared with similar patients in our general hospital population and analyzed for patterns of presentation, stage at diagnosis, degree of tumor differentiation, and survival. There was a higher incidence of poorly differentiated tumors in the young patients (21% vs. 8% in the general population). Colon cancer in young adults was in a more advanced stage at presentation. The survival rate for young patients was 23% vs. 61% for the general population (p = 0.02). Stage C patients treated for cure had a survival rate of 56% in the general population compared with 34% in young adults (p = 0.05). The degree of tumor differentiation did not affect survival in those young patients undergoing curative resections (41% for well-differentiated and 30% for poorly differentiated cancers, p = 0.09). The median survival time by stage was: Stage A and B (N = 3) 36 months, Stage C (N = 26) 32 months, and Stage D (N = 18) 15.8 months. The need for early recognition of colorectal cancer in young adults is emphasized by the greater incidence of advanced disease and the high failure rate.

Adult↗
PubMed1985

Surgical considerations in gastric cancer.

The American Joint Committee on Cancer staging system for gastric cancer is presented and its importance for defining prognosis and therapy is described. The report of the Gastrointestinal Tumor Study Group concerning adjuvant chemotherapy for gastric cancer is presented and the criteria for curative and noncurative resections are elucidated. The concepts of intraperitoneal chemotherapy, as an adjunct to aggressive surgical resection, is discussed.

Antineoplastic Agents↗
PubMed1984

Surgical oncology.

There has been a recent reassertion of the surgeon's role in cancer management. Traditionally, surgery has been the major modality of cancer treatment. In settings of clinical trials, surgeons had initially assumed a more passive status, contributing patients while chemotherapists and radiotherapists developed experimental protocols. Currently surgeons are taking an active role in planning and participating in such clinical studies. The American Joint Committee Staging System is being widely adopted, quality control of surgical procedures is improving, and innovative surgical operations are being devised. Surgical oncologists have spearheaded the concepts of multimodal treatment for their colleagues for a variety of cancers, most particularly cancers of the breast, head and neck, esophagus, lung, stomach, colorectum, and testicles, and sarcomas. The interaction of surgical treatment with radiation and chemotherapy is now more carefully planned, both for primary and metastatic tumors, and meaningful data are being derived from patient care. There is emphasis on treatment options, individualization of therapy, and restorative procedures at a variety of cancer sites. Constitutional aspects of cancer, such as nutrition, immune status, and metabolic aberrations, are given more attention, and there is a greater application of advances in cancer biology to the overall clinical care of patients.

Clinical Trials as Topic↗
PubMed1984

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.

Antigen-Antibody Complex↗
PubMed1984

Tumor-cell heterogeneity in soft tissue sarcomas as defined by chemoradiotherapy.

This report documents heterogeneous cell populations within high-grade soft tissue sarcomas in seven patients. The authors observed that, following chemoradiotherapy (five patients) or chemotherapy alone (two patients), surgically resected residual or recurrent sarcoma was found to be of low-grade histology. All chemotherapy was of Adriamycin (doxorubicin)-containing combinations. Seven other patients with regional recurrence after resection of high-grade sarcomas had high-grade recurrent tumors. Five of these patients had received no adjuvant therapy; two with extensive retroperitoneal liposarcomas and gross tumor-involved margins had received chemoradiotherapy. Follow-up ranged from 3 to 60 months (median, 12 months). These findings suggest that high-grade populations of sarcoma cells are more susceptible to chemoradiotherapy, as long as there is minimal residual disease. Low-grade clones of tumor cells may survive such therapy and present as clinical recurrence after initial treatment of low-grade or high-grade soft tissue sarcomas. Surgical resection is warranted for these recurrent lesions.

Adult↗
PubMed1984

Surgical management of locally advanced and recurrent breast cancer.

Considerations for surgical treatment of locoregional recurrences of breast cancer are particularly relevant at a time when many primary breast malignancies are being treated in a more conservative manner. The past experience with local recurrence after radical mastectomy was dismal: every patient with recurrence eventually developed systemic disease. Over 80% of such patients died within 2 years. The observations after local recurrence in patients with modified radical mastectomy are generally the same, although those with better prognostic lesions may have a marked delay in mortality. For patients with partial mastectomy and radiation, there are data which suggest that subsequent mastectomy for "in breast" recurrence may salvage approximately 50% of women and achieve long-term freedom from disease. This is a crucial question which will require more patients and time for confirmation. The author reviews patterns of locoregional recurrence after primary treatment of breast cancer, presents a plan for workup of such patients, and describes prognostic factors. The various treatment options, with their results, are discussed, and their dependency on the initial therapy is stressed. For patients with advanced Stage III primary breast cancer (T4 or N2, N3 lesions) and inflammatory carcinoma, a multimodal approach is proposed, with systemic multidrug chemotherapy as the initial treatment. The interlocking roles of surgical resection of the breast and radiation therapy must be considered, depending on the response to chemotherapy. Algorithms for therapy have been constructed to demonstrate the options.

Antineoplastic Agents↗
PubMed1984

Successful immunotherapy in a murine metastasizing fibrosarcoma model.

Antigenic differences were demonstrated between the primary murine fibrosarcoma and its metastases. Immunization with irradiated primary tumor cells (TC) protected C57B1/6J mice against subsequent challenge with those cells, but not against challenge with cells from pulmonary metastases (PMC). Mice immunized with irradiated PMC were protected from challenge with those cells, but not against challenge with TC. Mice with fibrosarcomas produced by the injection of 5 X 10(3) cells from the primary tumor were treated by resection of the tumor-bearing limb (Amp), Amp plus cyclophosphamide (Amp + Cy), Amp plus primary TC (Amp + TC), Amp plus primary TC and from its metastatic variant (Amp + TC + PMC), and with combinations of the last two groups with Cy. Although Amp + Cy improved survival, no animal lived 100 days and metastases increased as compared to controls. Immunotherapy significantly improved survival and decreased pulmonary metastases. Antigen combinations from primary and metastatic tumors resulted in significantly better survival than did a single preparation only from TC. Chemotherapy did not enhance the results obtained with immunotherapy and surgery. Immunity conferred in long-term survivors was permanent.

Animals↗
PubMed1984

The effect of 1,2-dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the Wistar Furth rat.

1,2-dimethylhydrazine (DMH)-induced colon cancer in Wistar/Furth (W/Fu) rats is analogous in many ways to human colorectal cancer. As part of our attempt to understand the immunobiology of these tumors, we have utilized the recently available monoclonal antibodies W3/25 and OX8 to monitor helper (Th) and suppressor (Ts) lymphocyte subpopulations. Normal untreated male W/Fu rats of less than 1 year of age were phenotyped (n = 43). The mean percentage of Th and Ts was 42 +/- 1 (mean +/- SEM) and 33 +/- 1, respectively. The mean Th/Ts ratio was 1.3 +/- 0.1. A Th/Ts equal to or greater than 1 is considered "normal" in the W/Fu rat. The DMH-treated rats (20 mg/kg/wk) were evaluated in initial experiments at various intervals after treatment. Rats studied 24 hours after a single DMH injection had no alterations in T cell subsets. Rats studied 28, 32, and 65 weeks after the start of 16 weekly DMH injections were found to have a decrease in the percentage of Th and a relative increase in Ts, with Th/Ts ratios of 0.6 +/- 0.2, 0.7 +/- 0.1, and 0.7 +/- 0.1, respectively (each P less than 0.01). In a separate experiment in which rats were studied after 4, 8, and 16 weeks of DMH injections, no alterations in T cell subsets were noted. Rats (n = 5) studied at 20 weeks after the start of DMH were found to have 41 +/- 3% Th and 36 +/- 2% Ts and a Th/Ts ratio of 1.2 +/- 0.1. Three of five rats were found to have adenocarcinomas. Four of five rats had Th/Ts less than 1. One rat with Th/Ts equal to 0.9 had metastatic disease. Rats studied at 25 weeks (n = 8) were found to have more advanced carcinomas (4/8) that were causing obstruction or bleeding in the animal. There was a significant decrease in Th and Ts in this group, with 24 +/- 3% and 26 +/- 3% respectively (P less than 0.001). The Th/Ts ratio for this group was 0.9 +/- 0.1 (P less than 0.01). In other experiments, rats were treated with DMH or placebo over a 16-week period and serially bled during and after treatment. No effect of DMH treatment on T cell subsets was noted. Repeated bleeding alone was noted to cause persistent alterations of T cell subpopulation.(ABSTRACT TRUNCATED AT 400 WORDS)

1,2-Dimethylhydrazine↗
PubMed1984

Colon and rectal carcinoma in the west of Scotland. Symptoms, histologic characteristics, and outcome.

Multiple clinical and pathologic factors have been analyzed retrospectively for a group of 456 patients with colon and rectal cancer treated in Glasgow over a span of 4 years. Sixty-five percent of these patients underwent curative resection, and another 16 percent had palliative resection. Obstruction and perforation (present in 19 and 5 percent, respectively) were associated with the highest operative mortality (17 percent for both) of any presenting symptom. However, when only patients who survived curative resection were considered, obstruction carried only a slightly lower 5 year survival than did other common symptoms, whereas perforation still led to only a 10 percent 5 year survival. Neither mucin production nor degree of differentiation influenced survival significantly. Adherence of the primary tumor to an adjacent organ was associated with a very poor prognosis (9 percent 5 year survival), but curative resection of the involved organs with the primary tumor increased the 5 year survival to 34 percent. Patterns of recurrence were noted to be markedly different for each primary site and for different stages. Dukes' stage was the most important overall determinant of prognosis.

Actuarial Analysis↗