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Biomedical subjects

M S Anscher

Publications and source records attributed to M S Anscher.

At least 73 records · Page 4Linked to original sources
PubMed1995

Changes in plasma transforming growth factor beta in response to high-dose chemotherapy for stage II breast cancer: possible implications for the prevention of hepatic veno-occlusive disease and pulmonary drug toxicity.

Veno-occlusive disease (VOD) of the liver and pulmonary drug toxicity (PDT) are two major complications of high-dose chemotherapy and autologous bone marrow transplantation (BMT) for solid tumors. We have previously demonstrated that an elevated plasma TGF-beta concentration before transplant predicts the later occurrence of these complications. In the present study, we used a simplified enzyme-linked immunosorbant assay (ELISA) to prospectively evaluate the kinetics of plasma TGF-beta concentrations of 45 patients with stage II breast cancer who underwent high-dose chemotherapy and autologous BMT. We demonstrated that, of the three TGF-beta isoforms, only TGF-beta 1 was present in the plasma. Pre-transplant plasma TGF-beta 1 was significantly higher in patients with VOD and PDT compared with that in patients without these complications. The plasma TGF-beta 1 level in patients who later developed VOD or PDT decreased to that of controls within 2 days of initiating high-dose chemotherapy; this decrease was not correlated with platelet concentration changes. These results suggest that interventions aimed at preventing the development at VOD or PDT must be given early in the course of high-dose chemotherapy.

Adenocarcinoma↗
PubMed1994

Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis.

PURPOSE: To determine whether plasma transforming growth factor-beta (TGF-beta) levels measured before and during radical radiotherapy for lung cancer could be used to predict patients at risk for the development of radiation pneumonitis. METHODS AND MATERIALS: The first eight patients with lung cancer (nonsmall cell: seven, small cell: one) enrolled in a prospective study designed to evaluate physiological and molecular biologic correlates of radiation induced normal tissue injury are described. The study began in June 1991. All patients were treated with radiotherapy with curative intent. Plasma transforming growth factor-beta levels were obtained before, weekly during, and at each follow-up after treatment. Pretreatment pulmonary function tests and single photon emission computed tomography scans were obtained to assess baseline lung function and were repeated at follow-up visits. Dose-volume histogram analyses were performed to determine the volume of lung which received > or = 30 Gy. Patients were assessed at each follow-up visit for signs and symptoms of pneumonitis. RESULTS: Five patients developed signs and/or symptoms of pulmonary injury consistent with pneumonitis and three patients did not. In all three patients not developing pneumonitis, plasma TGF-beta levels normalized by the end of radiotherapy. In contrast, four out of five patients who suffered pneumonitis had persistently elevated plasma TGF-beta levels by the end of therapy. This finding appeared to be independent of the volume of irradiated lung. CONCLUSIONS: These results suggest that plasma TGF-beta levels during treatment may be useful to determine which patients are at high risk of developing symptomatic pneumonitis following thoracic radiotherapy. This finding may have implications when planning additional therapy (either chemotherapy or radiotherapy) which may have potentially adverse consequences on the lung.

Adult↗
PubMed1993

Transforming growth factor beta as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer.

BACKGROUND: Hepatic veno-occlusive disease and idiopathic interstitial pneumonitis are major causes of morbidity and mortality after bone marrow transplantation. Fibrosis is a characteristic of both conditions, and transforming growth factor beta (TGF beta) has been implicated in the pathogenesis of fibrosis. METHODS: Using acid-ethanol extraction to remove TGF beta from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGF beta activity, we quantified plasma TGF beta in 10 normal subjects and 41 patients before and after they underwent high-dose chemotherapy and autologous bone marrow transplantation for advanced breast cancer. RESULTS: There was no difference in pretransplantation TGF beta levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGF beta levels were significantly higher in patients in whom hepatic veno-occlusive disease or idiopathic interstitial pneumonitis developed than in the controls or the patients without these conditions. The predictive value for the development of either condition was 90 percent or more when pretransplantation plasma TGF beta levels were more than 2 SD above the mean established in the controls. CONCLUSIONS: The plasma TGF beta concentration measured after induction chemotherapy but before high-dose chemotherapy and autologous bone marrow transplantation strongly correlates with the risk of hepatic veno-occlusive disease and idiopathic interstitial pneumonitis after these treatments.

Adenocarcinoma↗
PubMed1993

Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy.

OBJECTIVE: The authors determined whether microscopically positive surgical margins are detrimental to the outcome of early stage breast cancer patients treated with conservation surgery and radiation therapy. SUMMARY BACKGROUND DATA: The optimal extent of breast surgery required for patients treated with conservation surgery and radiation therapy has not been established. To achieve breast preservation with good cosmesis, it is desirable to resect as little normal tissue as possible. However, it is critical that the resection does not leave behind a tumor burden that cannot be adequately managed by moderate doses of radiation. It is not known whether microscopically positive surgical margins are detrimental to patient outcome. METHODS: The records of 259 consecutive women (262 breasts) treated with local excision (complete removal of gross tumor with a margin) and axillary dissection followed by radiation therapy for clinical stage I and II infiltrating ductal breast cancer at Duke University Medical Center and the University of North Carolina between 1983 and 1988 were reviewed. Surgical margins were considered positive if tumor extended to the inked margins; otherwise the margins were considered negative. Margins that could not be determined, either because the original pathology report did not comment on margins, or because the original specimen had not been inked were called indeterminate. RESULTS: Of the 262 tumors, 32 (12%) had positive margins, 132 (50%) had negative margins, and the remaining 98 (38%) had indeterminate margins. There were 11 (4%) local failures; 3/32 (9%) from the positive margin group, 2/132 (1.5%) from the negative margin group, and 6/98 (6%) from the indeterminate group. The actuarial local failure rates at 5 years were 10%, 2%, and 10%, respectively, p = 0.014 positive vs. negative, p = 0.08 positive vs. indeterminate (log rank test). Margin status had no impact on survival or freedom from distant metastasis; 63 patients who originally had positive or indeterminate margins were re-excised. Two of 7 with positive margins after re-excision versus 1/56 rendered margin negative had a local recurrence. CONCLUSIONS: The authors recommend re-excision for patients with positive margins because of improved local control of those rendered margin negative and identification of those patients at high risk for local failure (those who remain positive after re-excision). Because margin status impacts on local control, tumor margins after conservation surgery should be accurately determined in all patients.

Adult↗
PubMed1992

Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis. A phase I/II trial.

Patients undergoing x-ray therapy to the pelvis have intestinal symptoms proportional to the volume treated and the dose delivered. WR-2721, S-2 (3-aminopropylaminoethyl) phosphorothioic acid, is an organic thiophosphate compound that selectively protects normal tissues against radiation effects. A Phase I/II study was done to test the ability of topical application of WR-2721 to protect the mucosa of the rectosigmoid from radiation damage. Thirty-one patients were enrolled in this study, of which, seven were control subjects. Twenty-four patients received WR-2721 daily, in enema form, 45 minutes before treatment. The patients were assigned by groups of three to receive increasing doses of WR-2721 beginning with 100 mg/enema to 450 mg/enema. Rectal mucosal biopsies were obtained within the treated field before, during, and at the end of therapy. The degree of damage to the rectal mucosa was scored on the basis of a 0 to 4 scale (with 0, least damage to 4, most damage) as determined by the percentage of damaged mucosal crypt glands. The patients' symptoms were recorded once a week during the entire course of therapy. The biopsy scores of the control group were slightly higher than those of the treatment groups; however, this difference did not appear to be significant. In the treated groups, there was a slight decrease in the biopsy scores with increasing doses of WR-2721, but this trend was not sustained. There were no differences among any of the groups in the symptoms experienced during the course of therapy. This study showed that WR-2721 could be administered safely in enema form in doses ranging from 100 to 450 mg/enema, but this drug did not protect the rectosigmoid mucosa from radiation damage at the doses administered.

Administration, Topical↗
PubMed1992

Prognostic significance of extent of nodal involvement in stage D1 prostate cancer treated with radiotherapy.

The records of 107 patients with newly diagnosed adenocarcinoma of the prostate irradiated with curative intent at Duke University Medical Center from 1970 through 1983 were reviewed. Forty patients (37%) underwent standard bilateral pelvic lymph node dissection (PLND) prior to beginning irradiation. Twenty-four patients (22%) were found to have pelvic nodal metastases (Stage D1). Those found to have a single microscopically positive node at PLND may be curable with irradiation. In contrast, those with more extensive nodal metastases appear to be incurable with radiotherapy. Additional studies are needed to confirm or refute these findings.

Adenocarcinoma↗
PubMed1992

Radiotherapy for prostate cancer: should the seminal vesicles be considered target?

During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.

Adenocarcinoma↗
PubMed1992

Phase I/II study of external radio frequency phased array hyperthermia and external beam radiotherapy in the treatment of prostate cancer: technique and results of intraprostatic temperature measurements.

As part of an ongoing Phase I/II study at Duke University Medical Center investigating the toxicity and efficacy of external beam radiotherapy plus hyperthermia for deep-seated, locally advanced or recurrent solid tumors, 12 patients with prostate malignancies (adenocarcinoma--11, leiomyosarcoma--1) were treated with radiotherapy plus hyperthermia. Hyperthermia was given after radiotherapy using a Radio Frequency Phase/Amplitude Control Sigma 60 annular phased array device. All patients had simultaneous temperature measurements made in the rectal lumen and within the prostate during at least one hyperthermia session. Intraprostate thermometers were placed via a unique method described herein using both computerized tomography scan and a rigid sigmoidoscope for guidance. We were able to achieve the desired tumor temperature of > or = 42.5 degrees C in only 1/28 (3.5%) of hyperthermia treatments. Subjective symptoms of pain and/or pressure limited power deposition in 79% of hyperthermia treatments. Higher temperatures were achieved in the distal rectum than in the prostate in all treatments, although the differences were not statistically significant. This temperature differential could not be compensated by using phase and amplitude steering. Rectal temperatures adjacent to the prostate were predictive of prostate temperatures. We conclude that using this regional heating technique we were unable to demonstrate an ability to get an advantageous temperature differential between the prostate and normal tissue. This technique is not useful as an adjuvant to radiation therapy for prostate cancer. The usefulness of other regional heating techniques and devices should be explored.

Adenocarcinoma↗
PubMed1992

The role of radiotherapy in patients with advanced seminomatous germ cell tumors. Controversies in management. Part 2.

The role of radiotherapy in the management of advanced seminomatous germ cell tumors remains controversial. The authors review the available literature, and recommend radiotherapy for stage II seminoma with bulky abdominal metastases (greater than 10 cm) under the following circumstances: As primary therapy only if the patient cannot or will not be treated with chemotherapy; as an adjuvant following chemotherapy in patients with residual masses of any size. Similar recommendations are made regarding the role of radiotherapy in the management of extragonadal seminoma outside the central nervous system.

Dysgerminoma↗
PubMed1992

Radiation therapy for testicular seminoma: controversies in the management of early-stage disease.

Subdiaphragmatic irradiation remains the standard treatment for patients with stage I and IIA testicular seminoma. Elective mediastinal irradiation is not indicated. In well-selected patients with stage I disease, aggressive surveillance may be a reasonable alternative to elective irradiation. We believe that bipedal lymphangiography is useful in staging, radiation field design, and follow-up. Other controversies in the radiotherapeutic management include the optimal radiation dose and appropriate target volume.

Dysgerminoma↗
PubMed1991

Multivariate analysis of factors predicting local relapse after radical prostatectomy--possible indications for postoperative radiotherapy.

Between 1970 and 1983, 273 patients underwent radical surgery (radical prostatectomy--261, radical cystoprostatectomy--12) for newly diagnosed adenocarcinoma of the prostate at Duke University Medical Center and received no adjuvant radiotherapy. A total of 46 patients developed local recurrence. Forty developed local relapse only and six developed simultaneous local and distant failure. The crude local relapse rate was 17% (46/273). The actuarial local failure rate at 5, 10, and 15 years was 12%, 32%, and 35%, respectively. Univariate and multivariate analyses were performed to identify factors predictive of local relapse after radical surgery. Possible prognostic factors analyzed were: age, type of biopsy, use of adjuvant hormonal therapy, histologic grade, histologic involvement of seminal vesicles, positive surgical margins, clinical stage, and elevated acid phosphatase. Factors identified as significant predictors of local relapse by univariate analysis were: poorly differentiated histology (p = 0.0001), seminal vesicle involvement (p = 0.0009), and positive surgical margins (p = 0.0001). An elevated preoperative acid phosphatase was of borderline significance (p = 0.06). On multivariate analysis, poorly differentiated histology (p = 0.0007), positive margins (p = 0.0015), and elevated acid phosphatase (p = 0.0273) were significant predictors of local failure. Seminal vesicle involvement was no longer a significant predictor of local failure. However, on subsequent univariate and multivariate analyses, seminal vesicle involvement was the only significant predictor for the development of distant metastases (p = 0.0019, multivariate). Thus, patients with poorly differentiated tumors, positive surgical margins, or elevated preoperative acid phosphatase are at high risk for local relapse after radical prostatectomy. These patients should be included in future clinical trials studying the role of adjuvant radiotherapy after radical prostatectomy, or offered adjuvant radiotherapy if they cannot or will not participate in such trials.

Adenocarcinoma↗
PubMed1991

Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome.

From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial.

Actuarial Analysis↗
PubMed1991

The role of radiation therapy in the treatment of testicular germ cell tumors.

Infradiaphragmatic radiotherapy remains the treatment of choice for patients with stage I and II (small volume) testicular seminoma. With this approach, the disease-free survival rate exceeds 90% to 95%, and the ultimate disease-free survival rate (including salvage) is 95% to 100%. Initial therapy for patients with large-volume stage II, III, and IV disease should include multiagent systemic chemotherapy. Involved field radiotherapy is recommended for these patients following the chemotherapy, especially in patients with residual masses larger than a few centimeters. Although not used frequently in the United States, infradiaphragmatic radiotherapy is a viable treatment option for patients with clinical stage I testicular nonseminomas. Such therapy results in approximately an 85% to 90% relapse-free survival rate, with an ultimate survival rate (including salvage) approaching 100%. Initial therapy for patients with stage II or greater disease generally should include chemotherapy and/or surgery. Radiotherapy is often useful as post-chemotherapy consolidation, especially for unresectable masses. For extra-gonadal seminomas, radiotherapy is useful as definitive therapy for small-volume disease and as consolidative therapy (postchemotherapy) for more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Literacy and laryngectomy: how should one treat head and neck cancer in patients who cannot read or write?

The entire population of otolaryngologists and radiation oncologists (N = 192) in active practice in the state of North Carolina were surveyed to assess their level of awareness of illiteracy among adults in the United States and to determine whether these physicians consider illiteracy in the treatment decision process for patients with head and neck cancer. Excluding respondents who did not treat patients with head and neck cancer and physicians practicing outside of the state of North Carolina, the response rate was 115 of 182, or 63%. Only 26% of respondents were able to estimate correctly the prevalence of illiteracy in the US adult population. Forty-one percent of respondents, however, stated that they did consider their patient's ability to read and/or write before making treatment recommendations for head and neck cancer. This survey and accompanying literature review suggest that physicians perceive illiteracy as a problem that may have a significant impact on patients with head and neck cancer, but lack the data needed to enable them to quantify the effect of illiteracy on treatment outcome. The study reported is the first step in examining ways in which illiteracy might negatively affect patient outcomes.

Attitude of Health Personnel↗
PubMed1990

Transforming growth factor-beta 1 expression in irradiated liver.

The expression of transforming growth factor-beta 1 (TGF-beta 1) in the liver of irradiated rats was increased in a dose-dependent fashion 9 months after irradiation. Expression of TGF-beta 1 was confined primarily to hepatocytes in the pericentral region of the liver, and the percentage of hepatocytes strongly positive for TGF-beta 1 was significantly correlated with the extent of fibrosis. We further showed that a localized injection of TGF-beta 1 into normal rat liver elicited a strong fibrotic reaction at the injection site. These results suggest that the increased hepatic concentration of TGF-beta 1 in response to radiation injury may be important in the pathogenesis of radiation hepatitis. TGF-beta 1 was also found to be present at a significantly higher concentration in unirradiated human hepatocytes than in normal rat hepatocytes, implying that the propensity for humans to develop radiation hepatitis may result in part from the elevated levels of TGF-beta 1 normally found in human liver.

Animals↗
PubMed1989

Radiotherapy vs. hormonal therapy for the management of locally recurrent prostate cancer following radical prostatectomy.

Forty patients out of 273 who had undergone radical surgery for adenocarcinoma of the prostate at Duke University Medical Center between 1970 and 1983 developed palpable, biopsy-proven local recurrence without evidence of distant metastases. Of these 40 patients, 16 were treated with irradiation alone (Group I) and 16 patients were treated with hormonal therapy only (Group II). The remaining eight patients received either no therapy (4 patients) or both radiotherapy and hormonal therapy (4 patients) and are not further analyzed. Local control, as determined by palpation, was achieved in 14/16 patients in Group I versus only 7/16 patients in Group II (p less than 0.05). Subsequently, six patients in each group have relapsed, all with distant metastases. Thus, 8/16 patients in Group I remain alive without disease versus only 1/16 patients in Group II (p less than 0.05). There was no difference in survival between Groups I and II. No patient in either group has died free of disease. In Group I, 4/16 patients have died with cancer. Six of 16 in Group II have died with cancer. Severe complications occurred more frequently following irradiation compared to hormonal therapy. Irradiation appears to be superior to hormonal therapy in achieving local control and prolonging disease-free survival. Neither therapy conveys an advantage over the other in terms of survival. Thus, even if local control is achieved, distant failure may be an inevitable consequence of locally recurrent prostate cancer. Therefore, prevention of local recurrence after radical prostatectomy is of paramount importance. These findings support the use of adjuvant post-operative irradiation in patients at high risk for local recurrence.

Adenocarcinoma↗