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Biomedical subjects

M N Wesley

Publications and source records attributed to M N Wesley.

36 records · Page 2Linked to original sources

Resection of recurrent pulmonary metastases in patients with soft-tissue sarcomas.

Survival benefit and prognostic factors useful for patient selection have not been previously analyzed for patients with recurrent pulmonary metastases from soft-tissue sarcomas. Twenty-nine patients in our study had two or more resections of pulmonary metastases from 1976 to 1983. There were no operative deaths and three complications for 40 operations (7.5%). Factors predictive of increased survival following the second resection of pulmonary metastases were resectability and a disease-free interval of greater than six months from the first thoracotomy to the second recurrence in the lung. The tumor doubling time of the first recurrence and the presence of three or fewer nodules on full-lung tomography before the first thoracotomy, which were predictors of survival following initial resection, also predicted survival following subsequent resections. Overall median survival following the second resection was 14.5 months (22% overall three-year survival). The postresection actuarial survival curves for patients undergoing 1, 2, or 3 or more resections were not significantly different. Our findings demonstrate that patients undergoing repeated resections of pulmonary metastases from soft-tissue sarcomas can achieve prolonged survival.

Actuarial Analysis↗

Comparison of median sternotomy and thoracotomy for resection of pulmonary metastases in patients with adult soft-tissue sarcomas.

Thoracotomy and median sternotomy have both been advocated for resection of pulmonary metastases, and the advantages of each approach remain disputed. Patients with adult soft-tissue sarcomas undergoing resection of pulmonary metastases at the National Cancer Institute were studied retrospectively to assess the results of each surgical approach. Between 1981 and 1984, 65 patients underwent 78 sternotomies (7 lobectomies, 71 wedge resections); a mean of 9.5 nodules were resected per patient (range, 1 to 61). Resection of all nodules was accomplished in 60 of 71 explorations (84%) in patients with documented metastases. Benign lesions were found during 7 explorations (9%). Thirteen of 30 patients (43%) with unilateral metastases on linear tomography (LT), 45% (9 of 20) of patients with unilateral metastases on computed tomography (CT), and 38% (5 of 13) of patients with unilateral metastases on both CT and LT had bilateral metastases at sternotomy. Survival by type of incision was compared for 84 patients who underwent complete resection of their metastases (42 by sternotomy and 42 by thoracotomy); the minimum follow-up was two years. The groups did not differ significantly with respect to prognostic variables (tumor doubling time, disease-free interval, or number of nodules resected). There was no significant difference in actuarial survival between the two groups. The complication rate was 15% for the sternotomy group and 10% for the thoracotomy group (difference not significant). There were no operative deaths. Median sternotomy results in detection of unsuspected bilateral metastases and avoidance of a second operative procedure, but it does not increase operative morbidity or mortality or compromise overall patient survival.

Adult↗

Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery.

Fifty-one patients with stage IIIA or IIIB locally advanced breast cancer received primary induction chemotherapy (hormonal synchronization, 46 patients) to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response (CR) received radiation therapy, while patients with residual disease, partial response (PR), or stable disease (NC) received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide (500 mg/m2 iv) and doxorubicin (30 mg/m2 iv) on day 1; tamoxifen (40 mg/m2 orally) on days 2-6; Premarin (0.625 mg/m2 orally) every 12 hours for three doses, beginning on day 7; and methotrexate (300 mg/m2 iv) followed in 1 hour by 5-fluorouracil (500 mg/m2 iv) on day 8 and leucovorin rescue (10 mg/m2 orally) every 6 hours for six doses, beginning 24 hours after methotrexate. Fifty patients are evaluable with respect to response, time to disease progression, and survival. The rate of objective response to chemotherapy was 90%; 52% of the patients had CR, 38% had PR, and 10% had NC. The median numbers of chemotherapy cycles to achieve CR, PR, and NC were five, four, and four, respectively. Twenty-four patients with CR to chemotherapy were pathologically assessed, 22 by multiple biopsies and 2 by mastectomy. Seventy-one percent of the patients were proven to have pathological CR. All patients completing combined therapy thus far are disease free. Nine of 29 patients with stage IIIB disease have relapsed; 7 of 23 with inflammatory histology have relapsed; and 2 of 20 with stage IIIA disease have relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Differing determinants of prognosis following resection of pulmonary metastases from osteogenic and soft tissue sarcoma patients.

A study was performed to determine if prognostic factors could be used preoperatively to predict outcome following resection of metastases. Sixty-seven soft tissue sarcoma (STS) patients (median follow-up, 36 months) and 39 osteogenic sarcoma patients (OGS) (median follow-up, 29 months) underwent thoracic exploration at the first indication of pulmonary metastases, and the results for each group were reviewed. The number of metastatic nodules, disease-free interval (DFI), and tumor doubling time (TDT) significantly correlated with postoperative survival for STS patients. Patients with four or fewer nodules on preoperative linear tomograms survived longer (median, 23 months) than patients with more than four nodules (median, 6 months; P less than 0.005). Patients with a DFI greater than 12 months had a longer survival (median, 30 months) than patients with a DFI less than or equal to 12 months (median, 10 months; P less than 0.005). Patients with a TDT greater than or equal to 20 days had a longer survival (median, 22 months) than patients with a TDT less than 20 days (median, 6 months; P less than 0.005). The only significant predictor of survival for OGS patients was the number of nodules on preoperative linear tomograms (less than or equal to 4, 37 months median survival; greater than 4, 10 months median survival; P less than 0.05). This was due to significant differences noted for the DFI and TDT distributions between OGS and STS patients, with most OGS patients having a short DFI (less than or equal to 12 months) and a rapid TDT (less than or equal to 20 days) whereas STS patients had a more heterogeneous distribution (P less than 0.01). Thus, the number of metastases visible on the preoperative tomogram was the best predictor of survival for both OGS and STS patients. However, the applicability of other prognostic factors could not be generalized for these two closely related groups of patients.

Adolescent↗

Training and oncologists' changing attitudes toward their own cancer therapy.

Oncologists' attitudes toward therapy for his or her own hypothetical cancer have not been studied, and they may influence therapeutic decisions for patients. This study compared attitudes of oncologists at different levels of training toward therapy for their own hypothetical cancer. Those with limited oncology experience had high expectations for treatment, as expressed in their acceptance of all therapeutic modalities for their own disease. Early intensive inpatient oncology experience (first year of training) led to disenchantment, and rejection of various therapies. Further outpatient experience led to an increased acceptance of therapy again, and those finishing second and third year of oncology training, and senior medical staff in oncology, had high expectations for treatment. These results suggest an evolution of attitudes toward therapy with training and experience.

Attitude of Health Personnel↗

High-dose cisplatin in hypertonic saline.

To overcome the dose limiting toxicity of cisplatin we have administered high-dose cisplatin (200 mg/m2 body surface area in five divided daily doses with each dose administered in 250 mL of 3% saline) together with extensive hydration (250 mL/h normal saline with 20 meq KCI/L). In 17 previously untreated patients with poor prognosis nonseminomatous testicular cancer, 8 with tumor-associated obstructive uropathy, there was no statistically significant decrease in creatinine clearance or elevation of serum creatinine after three to four cycles of a high-dose cisplatin in combination chemotherapy regimen. High-dose cisplatin in combination with vinblastine, bleomycin, and VP-16 produced an 88% complete response rate in these high-risk patients who are characterized primarily by the presence of advanced bulky lung and abdominal disease. Six patients with ovarian cancer who had a relapse after treatment with standard dose cisplatin regimens were treated with high-dose cisplatin and three partial responses were seen. Four patients had no adverse effects on renal function whereas 2 patients had transient elevations in serum creatinine (4 to 5 mg/dL). Hypertonic saline did not provide protection against the nonrenal toxicities of cisplatin.

Adolescent↗

Analysis of prognostic factors in patients undergoing resection of pulmonary metastases from soft tissue sarcomas.

The selection of objective criteria that can reliably predict survival in patients undergoing resection of pulmonary metastases remains controversial. Between 1974 and 1982, 487 patients with soft tissue sarcomas presented to the National Cancer Institute. Eighty patients underwent thoracotomy for putative metastases and 67 patients had histologically proved pulmonary metastases. The 3 year tumor-free survival rate was 30% by actuarial analysis. Patients with resectable metastases had significantly prolonged post-thoracotomy survival compared to those patients with unresectable metastases. The most significant preoperative predictors of survival were the tumor doubling time, the number of metastases on preoperative linear chest tomograms, and the disease-free interval. Patients with a tumor doubling time of 20 days or more had a significantly longer post-thoracotomy survival (22 months median) than patients with a tumor doubling time of less than 20 days (6 months median). Those patients with four nodules or less on preoperative tomograms had significantly longer post-thoracotomy survival times (23 months median) than those patients with more than four nodules (6 months median). Patients with a disease-free interval of more than 12 months had a longer post-thoracotomy survival (32 months median) than patients with a disease-free interval of 12 months or less (10 months median). Combining these three prognostic factors significantly increased the predictive ability of this model. These criteria provide an accurate and rapid method to identify preoperatively those patients who will maximally benefit from resection of pulmonary metastases from soft tissue sarcomas.

Adolescent↗

Survival following aggressive resection of pulmonary metastases from osteogenic sarcoma: analysis of prognostic factors.

Between 1975 and 1982, 80 patients with osteogenic sarcoma were entered into prospective trials in the Surgery Branch of the National Cancer Institute. In 43 of these patients, pulmonary metastases developed as the initial site of recurrence, and 39 underwent one or more thoracotomies for resection of the disease. The actuarial five-year survival for the group of 43 patients with pulmonary metastases was 40%. Various prognostic factors were analyzed for their influence on survival after thoracotomy. Age, sex, location of primary tumor, tumor doubling time, and involvement of one or both lungs (bilaterality) were not significant in predicting survival. Prognostic factors that influenced survival, calculated by regression analysis, included the number of nodules on preoperative lung tomograms (negative correlation, p = 0.0004), disease-free interval (positive correlation, p = 0.0136), resectability (positive correlation, p = 0.002), and the number of metastases resected at thoracotomy (negative correlation, p = 0.0032). The presence of 3 nodules or less on preoperative full-lung linear tomography was found to be the single most useful preoperative prognostic factor. The application of these prognostic factors preoperatively may identify patients who will benefit optimally from thoracotomy.

Actuarial Analysis↗

A prospective randomized clinical trial of total parenteral nutrition in children with cancer.

A prospective randomized clinical trial was undertaken to test the efficacy of total parenteral nutrition (TPN) among previously untreated children receiving abdominal/pelvic irradiation with or without adjuvant chemotherapy who were at risk for weight loss, malnutrition, and complications from treatment. Children were evaluated by weight/height determinations, anthropomorphic measurements, and laboratory studies. TPN was associated with an improved nutritional status during therapy as compared with control patients on ad libitum intake. However, when TPN was discontinued, weight declined and there were no differences among treated and control patients detected at three-month follow-up. Likewise there was no obvious effect from TPN on tolerance to therapy in the adequately nourished child. TPN as initial supportive therapy should be reserved for those children who are malnourished or marginally malnourished at the time of presentation. Close nutritional assessment during treatment is essential since approximately 25% of children undergoing abdominal/pelvic radiotherapy with chemotherapy can be expected to become malnourished during an initial course of therapy.

Adolescent↗

Moderate dose methotrexate, vincristine, asparaginase, and dexamethasone for treatment of adult acute lymphocytic leukemia.

Thirty-eight adults with acute lymphocytic leukemia (ALL), 24 previously untreated and 14 previously treated, were entered into a study in which sequential, moderate-dose methotrexate and asparaginase were added to vincristine and dexamethasone (MOAD) for remission induction therapy. Eighteen of 24 previously untreated patients (75%) and 11 of 4 previously treated patients (79%) achieved a complete remission (CR). Once in CR, patients were given remission continuation therapy, which included intravenous high-dose methotrexate that was used without prophylactic cranial irradiation and without intrathecal methotrexate because of its potential activity alone as prophylaxis against central nervous system (CNS) leukemia. The median duration of CR was 11.1 mo (range 0.7-55.9+) and median survival 17.0 mo (range 0.4-55.9+) for the 24 previously untreated patients. The median duration of CR was 7.5 mo (range 1.9-55.3+) for the 14 previously treated patients. Only 2 of 24 previously untreated patients (8.3%) developed CNS leukemia at 3.3 and 42.7 mo from start of MOAD. None of the previously treated patients developed CNS leukemia as the initial site of relapse. MOAD is useful as induction therapy for previously untreated adults with ALL, as well as for previously treated patients, and is superior to other regimens that we have used for the treatment of adult ALL.

Adolescent↗

Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy.

The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

Adolescent↗

A study of the nutritional status of pediatric cancer patients.

The records of 455 children were reviewed to investigate the relationship of nutritional status at time of first referral to various measurements of disease and survival. Initial symptoms of weight loss, anorexia, fatigue, and early satiety were all directly correlated. Serum albumin level and nutritional status were not directly correlated. Likewise, there was no direct relationship between performance status and nutritional status. However, higher values of serum albumin were associated with better performance status. Nutritional status was directly related to freedom from relapse among children with solid tumors whether they had localized or non-localized disease. In addition, improved survival was related to good nutritional status for children with localized disease, whereas those with advanced disease had a poorer survival regardless of their nutritional status. Nutritional status appears to have prognostic implications among children with cancer.

Body Height↗

Long-term follow up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease.

Twenty-seven women previously treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone) chemotherapy were evaluated to determine the status of ovarian function. All patients had completed therapy a median of nine years earlier and had a median age of 30 years at the time of evaluation. Persistent amenorrhea has occurred in 11 of 24 patients (46 percent) treated with MOPP alone or MOPP plus radiation excluding the pelvis. Of patients with amenorrhea, 89 percent were older than age 25 at the time of treatment. In contrast, 80 percent of patients younger than age 25 at treatment continue to menstruate regularly. The time from diagnosis to amenorrhea was significantly shorter in the older patients (p = 0.001). Evaluation of serum gonadotropin and estradiol levels confirms ovarian failure as the cause of amenorrhea in all patients. Overall, these 27 patients have borne 13 normal children subsequent to chemotherapy. This long-term follow-up study demonstrates that chemotherapy-induced ovarian failure is age-related, that ovarian failure is often gradual in onset following the completion of chemotherapy and that, to date, the children born of women treated with this chemotherapy regimen appear to be entirely normal.

Adolescent↗

The role of H-2 in T cell recognition of Mls.

The role of H-2 was evaluated in T cell recognition of Mls-encoded antigens during primary mixed lymphocyte responses (MLR). Mlsc was used as a stimulating determinant in MLR and its recognition by T cells was assessed by linear regression analysis under culture conditions in which (A x B)F1 responder cell number was the factor limiting total response. Results of such experiments indicated the presence of distinct (A x B)F1 responder T cell subpopulations capable of differentially recognizing the foreign Mls antigen in association with one or the other parental H-2 haplotype. These findings demonstrate that T cells do not recognize Mlsc products in isolation, but rather are restricted to recognition of Mlsc in the context of "self" H-2 determinants.

Animals↗

Reasons for delay in breast cancer diagnosis.

BACKGROUND: A study of system delay, the time between the initial medical consultation and the establishment of a diagnosis, in breast cancer patients revealed that almost 40% of women reported delays of at least 4 weeks. The objective of this study was to explore the reasons for these prolonged intervals between initial medical consultation and establishment of a diagnosis. METHODS: A total of 367 female breast cancer patients from the National Cancer Institute's Black/White Cancer Survival Study were studied. Medical systems involved in the diagnosis and treatment of these women included hospital outpatient and emergency room, private clinic, public clinic, private doctor, and health maintenance organization. RESULTS: In about 25% of the cases, the delay was attributed by the woman to the patient herself, and the most common reason she gave was that she felt that the problem was not important. In about 45% of the cases, the provider and the health care system were said to be responsible for the delay through difficulties in scheduling or physician inaction, while in another 17% both the patient and the system were responsible. CONCLUSIONS: This study looked at the issue of how the behaviors of women and their providers contribute to the timing of breast cancer diagnosis. It is one of the only studies to examine the woman's role in delay. It is clear from this study that additional work is needed to look at this question. However, the results of this study suggest that efforts must be made to reduce the time needed to get an appointment with a physician or a diagnostic test, as well as to educate physicians and the women themselves regarding the importance of breast symptoms and the value of prompt evaluation, diagnosis, and treatment.

Adult↗

Value of prophylactic cranial irradiation given at complete remission in small cell lung carcinoma.

The optimal use of "prophylactic" cranial irradiation (PCI) in patients with small cell lung cancer remains undetermined. This study reviews the impact of PCI, given at complete remission (CR), on neurologic relapse in 172 consecutive patients with small cell lung cancer treated in three sequential chemotherapy protocols at the University of Maryland Cancer Center. In the first study of 38 patients, none received PCI. In the second study of 109 patients, the first 28 achieving CR were randomized to 3000 rad of PCI in ten fractions (PCI+) or to observation (PCI-). Thereafter, based on interim analysis, all patients achieving CR received PCI. In the third study, to date, 25 patients achieving CR have received PCI. Overall, 169 patients were evaluable for neurologic relapse, and 30 of 90 patients achieving CR received PCI. Among all patients with CR, with adjustment for disease extent, there was a significant delay to any neurologic relapse (P = 0.01) and cerebral metastases (P = 0.02) for PCI+ compared to PCI- patients. Among PCI- patients with CR, cerebral metastases alone occurred in 28% as the sole site and in 33% as the initial site, whereas cerebral relapse occurred prior to systemic relapse in only one PCI+ patient with CR. Patient survival however, was not significantly altered by PCI. PCI at CR confers effective and worthwhile local control in the CNS, especially during periods of systemic response, and a small percentage of patients may benefit. Systemic drug resistance still determines overall survival.

Adult↗

Ototoxicity and pharmacokinetically determined dosages of amikacin in granulocytopenic cancer patients.

Pharmacokinetic principles were used to determine amikacin doses for granulocytopenic cancer patients on empirical antibiotic regimens, and audiometry was used to determine the effect of this treatment on auditory acuity. Patients received ticarcillin 300 mg/kg/day plus amikacin, or moxalactam 8 g/day plus amikacin, in a blinded study. Amikacin doses were calculated to achieve a peak serum concentration (one hour after infusion) of approximately 25 micrograms/ml and a trough concentration of approximately 8 micrograms/ml. Baseline audiometry was conducted, and follow-up audiometry was done on completion of the antibiotic therapy. A decrease of greater than or equal to 20 db at any frequency in one or both ears was considered indicative of ototoxicity. Of 201 patients on the empirical antibiotic protocol, 55 had courses of treatment that could be evaluated. Ototoxicity not attributable to any other drug or disease process occurred in 10 patients. There were no significant differences related to age, weight, daily dose, or total dose between patients who developed ototoxicity and those who did not. Peak and trough amikacin concentrations were not significantly different between groups. More women than men developed ototoxicity. Duration of therapy for the ototoxic group was longer, and there was a trend for those with abnormal initial audiograms to develop further evidence of impairment. The significant risk factor for auditory toxicity was the combination of duration of aminoglycoside therapy and total dose per kilogram. Pharmacokinetically calculated doses of amikacin did not result in a higher incidence of auditory toxicity than reported in previous studies.

Adolescent↗