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Biomedical subjects

W S Fletcher

Publications and source records attributed to W S Fletcher.

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

Diagnosis and treatment of the inferior vena cava syndrome in advanced malignant disease.

The syndrome of intrahepatic inferior vena cava obstruction has neither been commonly recognized nor adequately described. Symptoms include the abrupt onset of ascites, hepatomegaly, and fluid retention below the diaphragm with edema of the lower extremity. Proteinuria can be associated with these symptoms. When this syndrome has been caused by malignant hepatic enlargement, it has not been well characterized in the literature, and its treatment has been ignored. We have diagnosed the inferior vena cava syndrome due to metastatic liver involvement in 34 patients before death. Thirty-three of these patients were treated using a combination of strip radiotherapy to the hepatic vena cava, with or without hepatic arterial infusion of chemotherapy. Fifty-six percent of the patients completed a full course of radiotherapy, with an 83 percent response rate. A dose of 3,000 to 4,500 rads was found to be safe and provided excellent palliation of ascites and edema. Tumors known to be radiosensitive had the best responses and side effects were few and mild in nature. Recognition and treatment of this condition will assume greater importance as survival is prolonged in more patients with advanced malignancy.

Breast Neoplasms↗
PubMed1986

Improved survival rates of patients with acral lentiginous melanoma treated with hyperthermic isolation perfusion, wide excision, and regional lymphadenectomy.

Twenty-three patients with extremity malignant melanoma who fit the clinical and pathologic criteria for acral lentiginous melanoma were treated in a prospective, nonrandomized trial of wide local excision, regional lymphadenectomy, and hyperthermic isolation perfusion. There were 17 patients (73.9 percent) pathologically judged to be in stage I and 6 (26.1 percent) in stage II. Three patients entered the study with regional recurrence. Delay in diagnosis of the lesions averaged almost 3 1/2 years. Increasing awareness about the occurrence of acral lentiginous melanoma may result in earlier diagnosis, increased survival rates, and cure. Life table survival analysis revealed 5 and 10 year survival rates of 75 percent and 58 percent, respectively. This supports the findings of Krementz et al and suggests not only that a marked improvement in survival can be achieved through the use of hyperthermic isolation perfusion, but that the survival of patients with acral lentiginous melanoma is comparable with that of patients with other extremity malignant melanomas treated with aggressive multimodality therapy.

Actuarial Analysis↗
PubMed1986

Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung. A Southwest Oncology Group Study.

Using a randomized prospective trial design, chemotherapy with 5-fluorouracil, vincristine, and mitomycin C (FOMi) was compared with cyclophosphamide, doxorubicin, and cisplatin (CAP) and with FOMi alternating with CAP (FOMi/CAP) in 452 eligible patients with metastatic large-cell undifferentiated and adenocarcinoma of the lung. Objective responses were obtained in 26%, 17%, and 22% of patients treated with FOMi, CAP, and FOMi/CAP, respectively. The median survival was similar for FOMi, CAP, and FOMi/CAP therapies (20, 24, and 23 weeks, respectively), but the overall survival (log rank test), 1-year survival, and remission duration were longer for FOMi/CAP-treated patients. Survival was significantly longer for fully ambulatory FOMi/CAP-treated patients compared with either FOMi (P = .01) or CAP (P = .04). Younger patients treated with full doses of therapy responded more often than older patients receiving reduced drug doses (26% and 11%, respectively; P = .003). A prognostic factor regression analysis of all eligible patients indicates that sex, performance status, stage, and treatment assigned were important independent variables determining survival (P less than .05). Toxicity was comparable in each treatment group.

Adenocarcinoma↗
PubMed1986

Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study.

Between 1977 and 1981, the Southwest Oncology Group entered 278 patients on a randomized study (SWOG 7703) to compare the effect of three different chemotherapeutic agents given in combination with radiotherapy (6000 rads over 7 weeks) following surgery for malignant gliomas. The chemotherapy regimens were: carmustine (BCNU)--80 mg/m2 iv daily X 3 every 6 weeks; procarbazine (PCB)--100 mg/m2 orally; or dacarbazine (DTIC)--175 mg/m2 iv daily X 5 every 4 weeks. Patients were stratified according to age, and degree of resection, with no differences identified between groups. The response rates (complete plus partial) for BCNU and DTIC were significantly better than for PCB [BCNU, 39%; PCB, 13%; and DTIC, 38% (P less than 0.01)]. The response duration and survival were somewhat better in patients treated with BCNU and DTIC, but compared to patients treated with PCB, the difference was not statistically significant. Median survival times were: BCNU, 45 weeks; PCB, 31 weeks; and DTIC, 49 weeks (P greater than 0.3). There were six toxic deaths with BCNU and four with PCB, most of which were due to infection associated with leukopenia. The high toxicity and minimal benefit of chemotherapy added to radiotherapy compared to historical results with radiotherapy alone suggest that combined treatment may not be indicated for some patients.

Brain Neoplasms↗
PubMed1986

Analysis of the risk reduction of prophylactic partial mastectomy in Sprague-Dawley rats with 7,12-dimethylbenzanthracene-induced breast cancer.

The effectiveness of prophylactic mastectomy in preventing breast cancer was studied in female albino Sprague-Dawley rats. Group A served as untreated controls. Groups B, C, and D underwent 50%, 75%, and total mastectomies 2 weeks after the administration of 7,12-dimethylbenzanthracene (DMBA). Group E was initially subjected to total mastectomy. Two weeks after surgery, group E received 5 mg of DMBA intravenously. Group F underwent sham procedures. All animals were sacrificed at age 8 months. The mean number of tumors per animal developing in groups A through E was 5.00, 5.17, 4.67, 5.46, and 5.20, respectively. There was 0.21 tumor per animal in group F. The mean time to tumor development in groups A through E was 11.33, 10.05, 9.88, 19.25, and 19.38 weeks, respectively. All results were subjected to an analysis of variance. There was no statistically significant difference in the number of DMBA-induced tumors in groups A through E. Groups D and E had a significant prolonged time to tumor development. The overall risk of the development of breast tumors was not significantly reduced by prophylactic mastectomy. Residual breast tissue after prophylactic mastectomy is at increased risk for the development of breast tumors. The risk of developing breast tumors in this model is not reduced in proportion to the amount of breast tissue removed. (This study suggests that subcutaneous mastectomy in high-risk individuals may not have appropriate prophylaxis against the development of carcinoma of the breast.)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Improved survival for soft tissue sarcoma of the extremities by regional hyperthermic perfusion, local excision and radiation therapy.

Soft tissue sarcomas continue to present problems with both local control of disease and death from distant metastases after accepted surgical therapy. Multimodality management has been established in the literature to be superior to traditional therapy of wide excision or amputation. The results of the treatment of 64 patients at Oregon Health Sciences University using regional hyperthermic perfusion with l-phenylalanine mustard and actinomycin D, wide local excision and external radiation therapy are reviewed. Histologic tumor types included: 19 liposarcomas, 14 malignant fibrous histiocytomas, eight fibrosarcomas, five leiomyosarcomas, four malignant schwannomas and 14 other sarcomas of the extremities. Minimum follow-up study has been 24 months and the mean follow-up time is more than five years. One-third of the patients presented with local recurrent disease after unsuccessful primary treatment. Over-all local recurrence for all patients treated by a combination of the aforementioned modalities was 3.4 per cent at two years and 11.1 per cent at five years. The over-all survival rate for all patients was 88 per cent at two years and 67 per cent at five years compared with a published over-all five year survival rate of 41 per cent. Patients with malignant fibrous histiocytomas had both two and five year local recurrence rates of 7.7 per cent and survival rates at two and five years of 79 and 63 per cent, respectively. This is compared with a previously published over-all five year survival rate with malignant fibrous histiocytomas of 46 per cent. The results with the treatment of liposarcomas were also superior to the published literature. Not only are the treatment results with regional hyperthermic perfusions excellent for both primary and locally recurrent sarcomas of the extremities, but limbs previously considered unsalvagable can be spared.

Adolescent↗
PubMed1985

Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA-directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty-two second-look patients remain free of disease 5 years after their second operation. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months.

Adenocarcinoma↗
PubMed1985

Breast carcinoma in situ. A retrospective review of 112 cases with a minimum 10 year follow-up.

We have retrospectively reviewed 112 cases of in situ carcinoma of the breast treated between 1960 to 1972, with a minimum 10 year follow-up to correlate treatment with outcome. We concluded that bilateral simple mastectomy with low axillary dissection is the treatment of choice for intraductal or lobular carcinoma in situ. This conclusion was based on the early age at diagnosis, the high incidence of bilaterality, and the long latency and probable progression from the in situ stage to the invasive stage. Lesser procedures can be endorsed for those patients of advanced age or who have associated medical problems whose life expectancy is estimated to be 10 years or less. Patients who refuse bilateral mastectomy should undergo biopsy of the involved or opposite breast at 3 to 5 year intervals regardless of physical findings or mammographic suspicions, especially when severe epithelial dysplasia is encountered in the biopsy specimens. This nonpalpable but potentially curable lesion remains difficult to detect even by mammography.

Adult↗
PubMed1985

Comparison of methotrexate and cisplatin for patients with advanced squamous cell carcinoma of the head and neck region: a Southwest Oncology Group Study.

One hundred eligible patients with inoperable, locally advanced or metastatic squamous cell carcinoma of the head and neck region following prior therapy were randomized to receive im methotrexate (50 patients) or iv cisplatin (50 patients). Methotrexate produced a complete plus partial response rate of 16.0% and cisplatin produced a partial response rate of 8.0%, with median durations of response of 18 and 8 weeks, respectively. The corresponding median survival times were 20 and 18 weeks. Methotrexate responders survived 60 weeks, versus 17 weeks for nonresponders. The corresponding survival times for cisplatin-treated patients were 38 and 18 weeks. Good pretreatment performance status had a significantly positive effect on survival (P = 0.04), but prior therapy did not. Toxicity secondary to either agent occurred with the expected frequency. The two agents examined showed comparable antitumor activity in patients with squamous cell carcinoma of the head and neck who had not previously received chemotherapy.

Adult↗
PubMed1984

Combined modality therapy for first recurrence of breast cancer. A Southwest Oncology Group study.

The Southwest Oncology Group has completed a study of 213 women with the first recurrence of breast cancer. Eligibility included a radical or modified radical mastectomy for cure and recurrence which had received no other form of therapy. Patients were started on tamoxifen (TAM) 20 mg daily (Phase I). Failures, or responders who subsequently failed, had an oophorectomy if the ovaries were intact, and TAM was continued (Phase II). During Phase III, eligible patients underwent an adrenalectomy, and lastly, in Phase IV, patients received chemotherapy. Responses to TAM were seen in 40% of 56 premenopausal patients, 46% of 95 postmenopausal women, and 44% of 62 patients without intact ovaries. Oophorectomy plus TAM gave responses only in premenopausal women who failed to respond on TAM or in postmenopausal patients who had a prior response to TAM. Adrenalectomy was successful in 7 of 21 patients. Chemotherapy resulted in 13% complete and 47% partial responses. Median overall survival was 108, 155, and 115 weeks, respectively, for the three patient groups. The authors believe that until results with chemotherapy improve significantly, hormonal therapy is the preferred first-line management of recurrent breast cancer.

Adrenalectomy↗
PubMed1984

Combination chemotherapy plus levamisole in the treatment of disseminated malignant melanoma. A Southwest Oncology Group study.

Two hundred-eighty patients were randomized to receive either BCNU, hydroxyurea and imidazole carboxamide (BHD), BHD plus levamisole, or high-dose DTIC plus actinomycin D. There was no difference in response rate in the three groups (24%, 25% and 22%). Females responded better than males and, as expected, those with a better performance status responded more favorably than those with poor performance status. Patients whose primary site of melanoma was on the extremities did significantly better than those melanomas originating on the trunk or head and neck. Patients with lymphocyte counts greater than 2000/mm3 fared better than those with lymphopenia. Those responders who received high-dose DTIC plus actinomycin D had a significantly longer length of response than those receiving the immunotherapy limb. This was also true in those patients who had a prior disease-free interval of greater than 6 months before being placed in this study. Although there was no difference in survival from the start of treatment in all patients, those patients receiving high-dose DTIC plus actinomycin D and who had a prior disease-free interval of greater than 6 months, had significantly superior survival when compared to the immunotherapy limb. It is concluded that the addition of Levamisole to BHD does not improve response rate and may in certain subsets be detrimental to disease-free response and survival. High-dose DTIC plus actinomycin D is equally effective to BHD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Percutaneous transhepatic biliary decompression. Results and complications in 30 patients.

The palliative management of malignant obstruction of the biliary tree continues to challenge clinicians. The technique of PTBD has become increasingly popular to decompress the obstructed biliary system. Our initial experience with 30 consecutive patients treated with PTBD has been retrospectively reviewed. Internal drainage and effective biliary decompression was achieved in 90 and 86 percent of patients, respectively. Complications developed in 7 of 11 patients with long-term PTBD. Two patients died from septic complications. Three of 10 patients had major complications associated with preoperative PTBD. The remaining seven patients had permanent PTBD but did not derive any clinical improvement. Postoperative mortality after palliative procedures for malignant biliary obstruction is most often associated with carcinomatosis and advanced disease. Palliative biliary bypass provides effective palliation until the patient's death. There are groups of patients with an expected survival of more than 3 months and technically bypassable biliary obstruction who are best palliated by biliary enteric anastomosis. Patients with advanced disease are not candidates for either form of treatment. In patients with lesions not suitable for surgical bypass, PTBD remains a useful alternative.

Adult↗
PubMed1984

The effectiveness of prophylactic subcutaneous mastectomy in Sprague-Dawley rats induced with 7,12-dimethylbenzanthracene.

Fifty-day-old female, albino Sprague-Dawley rats were induced with DMBA, a potent carcinogen that reliably causes multiple breast tumors. Prophylactic subcutaneous mastectomy was performed 2 weeks after injection. Control animals had no breast tissue removed and developed 5.14 tumors per animal, or 1.3 tumors per quadrant. Animals subjected to 50 percent (unilateral) mastectomy developed 5.4 tumors per animal, with 0.72 tumors per surgical quadrant. Animals that underwent 75 percent (three quadrant) mastectomy developed 4.33 tumors per animal, or 0.48 tumors per surgical quadrant. The incidence of tumors was significantly reduced in the surgical areas. However, the risk of any animal developing a breast neoplasm was not reduced in direct proportion to the percentage of breast tissue removed. We believe that this model may prove valuable in evaluating prophylactic subcutaneous mastectomy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Assessment of mutagenic damage following ethyl methanesulfonate mutagenesis in the axolotl (Ambystoma mexicanum).

When male axolots (Ambystoma mexicanus) were treated with 100 mg/liter of ethyl methanesulfonate (EMS), a dominant lethal effect was obtained. Embryonic survival of F1 progeny was most severely reduced between about 50 and 150 days after treatment. Dominant lethal lesions probably consist of chromosome breaks that lead to loss of parts of chromosomes or entire chromosomes. The appearance of embryos with a single nucleolus was used to assess this type of damage. The peak incidence of such embryos coincided with the peak of dominant lethality. At 25 mg/liter EMS, there was no significant dominant lethal effect, but as many as one-fourth of the embryos appeared morphologically abnormal during the period between 50 and 120 days after treatment. A small but significant number of embryos with a single nucleolus were also obtained. To assess possible recessive lethal damage, androgenetic haploids were produced from some of the mutagenized males. A broad trough of reduced haploid survival was obtained at 100 mg/liter, suggesting that damage is produced in most or all spermatogenic stages. At 10 mg/liter, where there was no dominant lethal effect or significant incidence of embryos with a single nucleolus, a broad period of reduced haploid survival was also obtained. Though we cannot exclude the possibility that chromosome abnormalities contribute to the reduced haploid survival, even at this low dose, the type of damage being assessed is almost certainly less severe than that leading to dominant lethality.

Ambystoma↗
PubMed1983

Geographic pathology of uterine cancers in Oregon: risks of double primaries and effects of socioeconomic status.

An intensive statewide study of uterine cancer incidence for the period 1968-1972 revealed that women with one histologic type of uterine cancer were much more susceptible to the simultaneous presence of a second histologic type than were the rest of the residents of the state. Squamous cell carcinoma was the most common uterine cancer; peak number and rate were found in the age group 25-29 years, indicating the need for periodic screening of young adult women and the need for discussion of neoplasia risk in adolescent sex education classes. Risks of squamous cell carcinoma and leiomyosarcoma were excessive among blacks. Socioeconomic status had a strong and consistent inverse relationship with uterine squamous cell carcinoma incidence, implying that its major risk determinant, sexual behavior, could have a similar socioeconomic pattern. Uterine adenocarcinoma incidence had a weaker but consistent direct relationship with socioeconomic status for which the cause is unknown.

Adenocarcinoma↗
PubMed1983

Adriamycin versus adriamycin plus cis-diamminedichloroplatinum (DDP) in advanced transitional cell bladder carcinoma. A Southwest Oncology Group study.

Patients with advanced transitional cell bladder carcinoma were randomized to receive either adriamycin alone, or adriamycin plus DDP. Overall response (CR + PR) was 8/41 (19%) for adriamycin alone versus 16/37 (43%) for the combination (p = 0.02). Median response duration was 14 weeks for adriamycin versus 25 weeks for the combination (p = 0.17). Median survival was 28 weeks on adriamycin versus 31 weeks on the combination (p = 0.82). Median survival of responders was 43 weeks, and for patients with stable disease it was 29 weeks. This was significantly better than for those with increasing disease at 15 weeks (p = 0.02). Increased frequency of leukopenia and gastrointestinal toxicity were seen with the combination. Cardiotoxicity and nephrotoxicity were not prohibitive.

Carcinoma, Transitional Cell↗