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Biomedical subjects

W S Fletcher

Publications and source records attributed to W S Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of octreotide acetate on pancreatic exocrine function.

Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.

Adult↗
PubMed1989

Effectiveness of prophylactic mastectomy in the prevention of breast tumors in C3H mice.

The effectiveness of prophylactic mastectomy in the prevention of breast tumors was studied in spontaneous breast-tumor-forming C3H mice. Prolactin levels were assayed to determine if this hormone was related to the incidence of mammary tumors. Two-hundred and fifty-six 1-month-old C3H mice were divided into four groups (control, 1; sham surgery, 2; mammectomy 50 percent, 3; and mammectomy 100 percent, 4). At the time of sacrifice (0 to 1 year postoperatively) estrus cycles were determined, ventral skin (breast) and ovaries were removed for histology, and serum was collected for prolactin assays. Prolactin levels 24 hours postoperatively were significantly elevated (p less than 0.01) in groups 2 to 4 when compared with group 1. Six months postoperatively, prolactin levels were significantly higher (p less than 0.05) in mice with tumors compared with those without tumors in groups 3 and 4. There were no differences in tumor incidence between the four groups. At 12 months postoperatively, no differences in prolactin levels were noted, but group 2 animals had the highest incidence of mammary tumors (89 percent; p less than 0.01) when compared to groups 3 and 4. Mammary tumor incidence was not decreased by 50 percent or 100 percent mammectomy in C3H mice. Prolactin levels rose in response to surgery and/or anesthesia and remained elevated only in tumor-bearing mice who underwent mammectomy, an occurrence similar to that reported in humans.

Adenocarcinoma↗
PubMed1988

Nonanatomic hepatic resection for secondary hepatic tumors with special reference to hemostatic technique.

The techniques for resection of hepatic tumors have traditionally been based on lobar anatomy. The morbidity and mortality associated with hepatic resection have been most closely correlated with intraoperative blood loss. The results of 37 hepatic resections for secondary neoplasms were retrospectively reviewed. This group included 18 patients who underwent anatomic resections and 19 patients who underwent nonanatomic resections. The nonanatomic group experienced significantly less blood loss, shorter operating times, shorter hospital stays, and no significant difference in long-term survival. A positive relationship between blood loss and postoperative complications is demonstrated for the combined groups. These results support the use of nonanatomic resection whenever feasible for secondary hepatic tumors. We describe the technique for nonanatomic hepatic resection for metastatic lesions, with special emphasis on hemostatic techniques.

Adult↗
PubMed1988

VP-16 + adriamycin vs. adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study.

One hundred twenty-two patients with advanced adenocarcinoma of the breast were randomized to receive adriamycin (AD) alone or a combination of VP-16 plus lower dose adriamycin (VAD). The patients were stratified to good and poor risk. The starting dose (day 1) of AD was 60 mg/m2 for good risk and 45 mg/m2 for poor risk. The starting dose of the VAD combination for the good-risk patient was VP-16, 75 mg/m2 daily x 5 plus adriamycin 35 mg/m2. The poor-risk dose for VAD was VP-16, 50 mg/m2 daily x 5 plus adriamycin, 30 mg/m2 on day 1. The total dose of AD was 450 mg/m2 on both arms. The patients who were on the VAD arm continued on VP-16 maintenance. Both arms were repeated every 21 days. There were 54 evaluable patients on the adriamycin arm and 52 evaluable patients on the VAD arm. Both arms were similar with regard to age, menopausal status, performance status, and prior hormonal therapy. More hematologic toxicity was seen in the adriamycin arm. Complete responses were observed on both arms, three (5%) with adriamycin and three (5%) with combination. Eleven (19%) and ten (18%) partial responses were observed with the adriamycin and VP-16 plus adriamycin, respectively. AD produced more stable disease than VAD (41% vs. 29%). Complete responses were seen only in the good-risk patients. Time to progression was delayed on the combination arm (P = 0.02). The survival in both arms was similar. The addition of VP-16 to adriamycin does not offer an important clinical advantage.

Adenocarcinoma↗
PubMed1988

Phase I-II pilot of whole abdominal radiation and concomitant 5-FU as an adjuvant in colon cancer: a Southwest Oncology Group Study.

Thirty-eight patients with Stage B2, C1 or C2 colon cancer (Astler-Coller Modification of Dukes) received 3000 rads whole abdominal radiation and concomitant intermittent bolus 5-FU as part of a phase I-II adjuvant trial. Patients whose tumor penetrated the serosa (B2 or C2) in addition received a 1600 rad boost to the tumor bed. 5-FU was administered only during radiation. It was given at a dose of 300 mg/m2 days 1-5 and 28-32 in 21 patients (Group A) and day 1-3 and 28-31 in 17 patients (Group B). Median follow-up time for Group A is 44 months. Group A patients have a disease-free survival of 66% and overall survival of 73% at 44 months. The 16 C2 patients in Group A have a disease-free survival of 54% and overall survival of 65% at 44 months. There was a 26% incidence of moderate to severe acute toxicity in Group A but no long term bowel, liver, or hematologic toxicity. One patient developed acute myelogenous leukemia 2 years after treatment. Group B patients had only a 6% incidence of moderate to severe toxicity, but had a disease-free survival of 60% and overall survival of 100% at median follow-up of 23 months. Group B Stage C2 patients had a disease-free survival of 53% and overall survival of 100% at this same follow-up period. Disease-free and overall survival in Group A Stage C2 patients is superior to that in several published trials. Given the manageable toxicity, adjuvant whole abdominal radiation with concomitant 5-FU and tumor bed boost should be tested in a randomized fashion for possible therapeutic benefits.

Abdomen↗
PubMed1988

Synergistic cytotoxicity between dimethyl sulfoxide and antineoplastic agents against ovarian cancer in vitro.

Dimethyl sulfoxide is a well-known differentiating agent that has been shown to inhibit tumor growth in vitro. We hypothesized that antineoplastic agents might show synergistic cytotoxicity when combined with 10% dimethyl sulfoxide. Twenty-four malignant ovarian tumors were removed and used in tests to determine the cytotoxicities of 10% dimethyl sulfoxide alone, each of six antineoplastic agents alone, and 10% dimethyl sulfoxide plus each antineoplastic agent. Cytotoxicity results for 10% dimethyl sulfoxide alone and each antineoplastic agent alone were used to evaluate each combination of dimethyl sulfoxide and an antineoplastic agent for synergy. There were 14 synergistic responses that were statistically significant at the p less than 0.01 confidence level between 10% dimethyl sulfoxide and an antineoplastic agent against the ovarian tumors. Seven of these responses were significant at the p less than 0.0003 level. This is strong evidence that true synergistic cytotoxicity occurs when an antineoplastic agent is combined with 10% dimethyl sulfoxide. We conclude that intraperitoneal delivery of antineoplastic agents in 10% dimethyl sulfoxide may be useful in the treatment of certain ovarian cancers.

Anthraquinones↗
PubMed1988

Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities.

Fifty-nine patients with melanoma or soft tissue sarcoma of the extremities underwent hyperthermic isolated limb perfusion utilizing cisplatin and wide local excision. Doses of cisplatin ranged from 0.75 to 2 mg/kg. The mortality and morbidity rates were 0 and 6.8 percent, respectively. Pharmacokinetic studies indicate that cisplatin is rapidly bound to perfused tissues and remains bound for 1 month. Maximum tumor response in sarcomas occurs 1 to 2 weeks after perfusion, compared with 1 month after perfusions with l-phenylalanine mustard and actinomycin D. Local and regional recurrence rates were 0 and 3.4 percent, respectively, at 1 year. Further studies of hyperthermic limb perfusions with cisplatin are warranted.

Adult↗
PubMed1988

Cytotoxicity of dimethyl sulfoxide and antineoplastic combinations against human tumors.

Five human tumor reference cell lines were tested in vitro against 0 percent, 5 percent, and 10 percent DMSO; four antineoplastic agents; and combinations of 5 percent or 10 percent DMSO plus each antineoplastic agent. Synergistic cytotoxicity between DMSO and antineoplastic agents against each cell line were demonstrated. We have concluded that delivery of standard doses of antineoplastic agents in 5 percent or 10 percent DMSO may be useful in the treatment of some tumors because of the marked increase in tumoricidal effect seen with some DMSO and drug combinations. Alternatively, lower doses of antineoplastic agents might be delivered in DMSO, producing the same cytotoxic effect as a full dose of drug without DMSO but with less systemic toxicity.

Antineoplastic Agents↗
PubMed1988

Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects.

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.

Adult↗
PubMed1988

Evaluation of cis-platinum and DTIC combination chemotherapy in disseminated melanoma. A Southwest Oncology Group Study.

The development of disseminated melanoma is associated with an extremely poor prognosis. Use of a variety of chemotherapy agents alone and in combination has yielded response rates of only 10-30%. Surgery and radiation therapy play a useful role in palliative treatment, but have little or no value in the treatment of disseminated disease. In order to evaluate the response of disseminated malignant melanoma to combination chemotherapy with cis-platinum and 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC), a phase II pilot study was developed and conducted at Oregon Health Sciences University. Thirty patients were treated from January 1983 to October 1986 and evaluated. There were two complete responses (7%) and nine partial responses (30%) for a total response rate of 37%. The median duration of response was 31 weeks. This response rate is higher than has been previously achieved with DTIC and cis-platinum, or with other drugs alone or in combination. Severe (grade 3) renal, neurologic, and hematologic toxicity was seen in four of 30, three of 30, and ten of 30 patients, respectively.

Adult↗
PubMed1988

Suppression of primary and secondary peptides with somatostatin analog in the therapy of functional endocrine tumors.

Sandostatin (SMS 201-995 (SMS)), a potent, long acting analog of native somatostatin was used in five patients with functional endocrine tumors (gastrinoma, two patients; insulinoma, one patient; glucagonoma, one, and adult onset nesidioblastosis, one). Primary and secondary peptide levels were obtained during provocation with a test meal, a calcium infusion, a secretin bolus and either a glucagon or tolbutamide bolus. During provocation test, the levels of the primary peptides insulin and C-peptide (nesidioblastosis and insulinoma), gastrin (gastrinoma), glucagon (glucagonoma) and the secondary peptides calcitonin, gastrointestinal peptide, gastrin releasing peptide, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance-P and vasoactive intestinal peptide were obtained at predetermined intervals and quantitated by radioimmunoassay. SMS therapy was begun and peptide levels were again obtained during provocation. SMS suppressed basal primary peptide levels in all patients by more than 50 per cent. In 23 of 26 provocative tests, SMS effectively decreased circulating peptide levels by more than 50 per cent. Thirteen instances of elevated basal secondary peptides were discovered, and SMS universally suppressed these levels by a mean of 54 per cent. Of the 44 provocative tests performed, elevated secondary peptide levels were present in 41. SMS was effective in 31 of these 41 tests. The mean suppression of these provoked secondary peptide levels was 70 per cent. SMS effectively suppresses both basal and provoked peptides and, thus, provides relief of the clinical symptoms induced by pathologic elevations of primary and secondary peptides.

Adenoma, Islet Cell↗
PubMed1987

The mechanism of hormone-sensitive breast cancer progression on antiestrogen therapy. Implications for treatment and protocol planning.

Fifteen patients whose tumors progressed while they received tamoxifen citrate therapy were studied by serial determinations of serum levels of estrone (E1), estradiol (E2), and dehydroepiandrosterone (DHEA) obtained during progression after withdrawal from tamoxifen therapy and total endocrine ablation or suppression. Discontinuation of tamoxifen therapy resulted in reductions of DHEA, E1, and E2 levels by 44%, 49%, and 42%, respectively. Ablation or suppression reduced sex steroids to minimal levels and produced responses in all patients. Elevations of DHEA, E1, and E2 could be provoked by readministering tamoxifen to hypophysectomized and oophorectomized, but not adrenalectomized, patients, indicating that the adrenal gland is the source of these sex steroids. We conclude that tamoxifen stimulates adrenal production of DHEA, which is aromatized to E1 and E2. Buildup of E1 and E2 overwhelms the competitive binding of tamoxifen to the estrogen receptor, resulting in tumor progression.

Adrenal Glands↗
PubMed1987

Response of advanced breast cancer to total endocrine ablation after exacerbation on tamoxifen: results in seven patients and possible mechanism of action.

Usage of tamoxifen in the treatment of advanced breast cancer is increasing and is advocated by some authors as primary therapy in all estrogen receptor positive cancer patients. Tamoxifen is an incomplete estrogen antagonist with partial estrogen agonist activity as well. Tamoxifen-induced exacerbation of breast cancer ("tamoxifen flare") is reported to occur in 4-20% or more of treated patients. Management of this condition has varied from stopping treatment to continued administration or reinstitution of tamoxifen after flare symptoms subside. Responses have occurred in some patients so treated, although the remissions do not appear durable. The seven patients with advanced breast cancer in this report experienced disease exacerbation with tamoxifen therapy. Endocrine ablation afforded all patients excellent pain relief and disease control with prolonged survival in six of the seven. There have been no studies directly examining the disease course in flare patients continuing on tamoxifen. Persistence in treating these patients with an incomplete antagonist-agonist may deprive them of full survival benefit possible through ablative procedures when used in sequential treatment.

Adrenalectomy↗
PubMed1987

Improved survival of patients with stage II melanoma of the extremity using hyperthermic isolation perfusion with 1-phenylalanine mustard.

Between 1964 and 1983, 65 patients with Stage II extremity melanoma were treated in a nonrandomized fashion with wide local excision, lymph node dissection, and hyperthermic perfusion with 1-phenylalanine mustard at 1.0-1.5 mg/kg. Southwest Oncology Group Stage II criteria were used, including IIA (node positive), IIB/C (recurrent local/regional), or both. During the study interval, literature reports of 5-year survival for Stage II melanoma ranged from 6% to 50% and averaged approximately 26% to 30%. In this study group, 40% of patients had recurrent disease confined to regional lymph nodes, 33% had recurrent cutaneous disease, and 26% had recurrent disease in both locations. Survival for all Stage II patients at 5 years was 56.6%, and 40% at 10 years. When recurrent disease was confined to regional nodes only (IIA), survival at 5 years was 70.5%, and 40% at 10 years. Survival for patients with Stage IIB/C disease at 5 and 10 years was 58% and 43.7%. When recurrent melanoma was present in both skin and nodes, 5-year survival was 29%. The present study indicates that aggressive treatment of Stage II extremity melanoma, which includes hyperthermic isolation perfusion, can prolong survival in these high-risk patients.

Arm↗
PubMed1987

Phase II evaluation of bisantrene hydrochloride in refractory malignant melanoma. A Southwest Oncology Group Study.

Patients with a pathologically proven diagnosis of malignant melanoma were entered into a phase II trial of bisantrene. Eligibility criteria included: measurable, metastatic disease; performance status 0-2 SWOG; and adriamycin total cumulative dose of less than 400 mg/m2. The initial bisantrene dosing schedule was 260 mg/m2 every three weeks for good risk patients. Due to the absence of an objective response and the lack of severe toxicity in the first 25 bisantrene treated patients, the starting dose was increased to 300 mg/m2 for good risk patients. Fifty-one patients received a median of two bisantrene courses (range 1-11 courses). Leukopenia was the major toxicity. Fifteen (68%) of the 22 good risk, intermediate dose patients (260 mg/m2), and 8 (80%) of the 10 good risk, high dose patients (300 mg/m2) evaluable for toxicity experienced mild-severe leukopenia. None of the 51 patients experienced a complete or partial response to bisantrene. Median survival was 3.3 months. We conclude that bisantrene is ineffective in the treatment of metastatic melanoma.

Adult↗
PubMed1987

Hepatic resection for primary and secondary neoplasms of the liver.

Fifty consecutive major hepatic resections were performed for primary and secondary malignant neoplasms of the liver. There were 7 children and 9 adults with primary neoplasms and 34 patients with secondary neoplasms. The mortality rate was 0 percent and the morbidity rate, 14 percent. Postoperative morbidity correlated with operative blood loss. The 5 year survival rates for children and adults with primary neoplasms were 42 percent and 22 percent, respectively, and the 5 year survival rate for adults with secondary neoplasms was 15 percent. Factors such as disease-free interval, number of metastases, and stage of metastases did not influence the postoperative survival rate. Also, there was no difference in survival rate between patients whose metastases were resected by lobectomy or segmentectomy and those whose metastases were resected by wedge resection.

Adenoma, Bile Duct↗
PubMed1986

A useful high-dose intermittent schedule of adriamycin and DTIC in the treatment of advanced sarcomas.

One-hundred-fourteen evaluable patients with metastatic soft tissue or bony sarcoma with measurable disease were treated with Adriamycin (doxorubicin) administered intravenously at a dose of 60 mg/M2 on day 1, followed by DTIC (dacarbazine) at a dose of 750 mg/M2; courses were administered at 3-week intervals. Ten complete remissions and 17 partial remissions were observed. The most responsive cell type was malignant fibrous histiocytoma with a response rate of 54%. This treatment schedule was very well tolerated, with only moderate myelosuppression and moderate nausea and vomiting. Cardiac toxicity was identified in three patients, with two patients demonstrating electrocardiogram (EKG) changes and arrhythmias and only one patient developing heart failure. The 24% overall response rate suggests no compromise in activity on this schedule, with a significant reduction in toxicity.

Antineoplastic Combined Chemotherapy Protocols↗