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Biomedical subjects

A Eisbruch

Publications and source records attributed to A Eisbruch.

53 records · Page 3Linked to original sources

Adjuvant irradiation after prostatectomy for carcinoma of the prostate with positive surgical margins.

BACKGROUND: Patients with adenocarcinoma of the prostate treated with prostatectomy who have tumor at the margins of the surgical specimen or tumor involvement of the seminal vesicles have a high risk of local recurrence and metastatic disease. It is unclear whether postoperative irradiation improves their outcome. METHODS: This is a retrospective analysis of patients treated with prostatectomy for adenocarcinoma of the prostate who had surgical margins or seminal vesicles involved by tumor. Thirty-four patients received adjuvant postoperative irradiation (Group 1), and 43 patients did not receive irradiation (Group 2). RESULTS: The tumor control rates in the prostatic bed for patients who had radical prostatectomy were 100% and 84% in Groups 1 and 2, respectively (P = 0.017). Actuarial 10-year disease-free survival from the date of prostatectomy was 46% and 55% for Groups 1 and 2, respectively. CONCLUSIONS: Adjuvant irradiation after prostatectomy in patients with positive surgical margins or seminal vesical invasion increases prostatic bed local tumor control but does not affect survival. Postoperative irradiation is associated with acceptable morbidity.

Adenocarcinoma↗

Estimation of tissue volume irradiated by intracavitary implants.

PURPOSE: The volume of space enclosed by a specified isodose surface arising from an intracavitary implant may correlate with clinical outcome. Several investigators have proposed using the product of the three maximum orthogonal dimensions of the isodose surface as a measure of this volume. We have examined the accuracy of this proposal and compared it to a simpler model for estimating volume which requires only knowledge of the mgRaEq-hrs (total reference air kerma) and the dose level. METHODS AND MATERIALS: Orthogonal films from 204 intracavitary implants of 128 patients with carcinoma of the cervix were used to reconstruct the 137Cs-source coordinates. The source location, strength and duration data were used to calculate dose-volume histograms, yielding the volume enclosed by each dose level as well as its orthogonal dimensions: thickness, width, and height. Using bony landmarks to align films for different insertions in the same patient, similar calculations were repeated for composite implant source coordinates. RESULTS: Curve-fitting techniques revealed that the volume encompassed by each isodose level could be predicted by a modified power-law function of the mgRaEq-hr/dose ratio: predicted volume = [104.8 - 8.103.(M/D) + 0.437.(M/D)2].(M/D)1.635 where M/D = mgRaEq-hr/cGy. The volume predicted by this simple model is accurate within +/- 10% in 95% of the implants when mgRaEq-hr/cGy = 0.8. Accuracy increases with increasing mgRaEq-hr/cGy. In contrast, the ratio, product of orthogonal dimensions/actual volume, varies widely from implant-to-implant, as well as differing systematically from one implant type to another. Investigation of the individual orthogonal dimensions demonstrated that width and height, but not thickness, were moderately well correlated with corresponding maximum implant dimensions. However, in all cases the dimensions were more sensitive to changes in mgRaEq-hr/cGy than to changes in implant geometry. CONCLUSIONS: The product of the orthogonal dimensions is an unsatisfactory estimator of the actual irradiated volume encompassed by an isodose surface. Isodose surface volumes can be accurately estimated knowing only mgRaEq-hr. Prescribing intracavitary brachytherapy by mgRaEq-hr, or its derivative, total reference air kerma, is equivalent to requiring that an isodose surface encompass a specified volume which does not depend on the implant geometry. Constraining the mgRaEq-hr delivered therefore serves to limit the volume of tissue irradiated to high doses.

Brachytherapy↗

Irradiation in relapsing carcinoma of the prostate.

BACKGROUND: Radiation therapy plays a major role in the management of patients with either locally recurrent or metastatic carcinoma of the prostate. RESULTS: In 23 patients with isolated postprostatectomy local recurrences treated with doses of 60-65 Gy, 17 (74%) had tumor control, and 45% survived relapse-free for 5 years after treatment of the recurrence. Pelvic irradiation has been used to treat patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy. This was tried, and 17 of 24 patients (70%) showed a significant decrease in PSA levels after irradiation, in five without subsequent elevation. Two of the seven patients with elevated PSA levels later had distant metastases. Local irradiation has been reported to yield excellent relief of symptoms in 100% of patients with hematuria, 80% with urinary outflow obstruction, and 50-70% with ureteral obstruction or pelvic pain secondary to locally advanced prostatic carcinoma. Reirradiation, particularly with brachytherapy (in preliminary studies combined with hyperthermia) has been used in the management of postirradiation prostatic recurrences with satisfactory tumor regression in approximately 75% of patients. The Radiation Therapy Oncology Group (RTOG) reported on the palliative effects of external irradiation on patients with bony metastasis. Approximately 54% of such patients had complete relief, and 29% had partial relief of bone pain. However, the retreatment rate of the bony metastasis was lower in the patients receiving higher doses. In a RTOG protocol in which all patients received local irradiation for osseous metastases, 77 were randomized to receive elective hemibody irradiation and 69, local treatment only. The frequency of additional treatment at 1 year was lower in the hemibody irradiation group (54% versus 78%). Occasionally, brain, mediastinal, or liver metastasis can be treated with irradiation. Radioactive phosphorus-32 or strontium-89 has been administered for disseminated bony metastasis with improvement of bone pain in approximately 70-80% of treated patients. CONCLUSION: The role of irradiation in the treatment of spinal cord compression is discussed. Significant improvement of neurologic function has been reported in 36-60% of the patients, depending on severity of deficit and promptness in instituting emergency treatment.

Bone Neoplasms↗

Role of Postradical Prostatectomy Irradiation in Carcinoma of the Prostate.

The indications and results of postradical prostatectomy adjuvant pelvic radiation therapy (6,000 to 6,500 cGy) are reviewed. In patients with positive with positive surgical margins, 80% to 100% local tumor control has been reported; in 42 patients treated at our institution, the 5-year actuarial tumor control rate was 85%. Most authors report higher disease-free survival (DFS) rates in patients receiving adjuvant postoperative irradiation for positive margins (70% to 80% at 5 years and 50% to 70% at 10 years) compared with nonirradiated patients (50% at 5 years and 40% at 10 years). However, more difficult to document and never indisputably reported has been the improvement in overall survival (OS) rates with adjuvant irradiation; the actuarial survival rates, 75% to 80% at 5 years and 45% to 60% at 10 years, are comparable to those of nonirradiated patients. Results have been published on patients with positive pelvic lymph nodes (stage D1) following pelvic irradiation (6,000 to 6,500 cGy). At our institution, the 5-year DFS rates were 60% in 22 patients without extracapsular tumor extension and 20% in 34 patients with perprostatic involvement. In 24 patients with postprostatectomy persistently or subsequently elevated prostatic specific antigen (PSA) levels, preliminary analysis showed initial 79% decrease in PSA level after pelvic irradiation (6,000 to 6,500 cGy), although only 70% of the patients have sustained such decreased levels. Patients with persistent or subsequent elevation of PSA after irradiation have a high incidence of distant metastases (50%). There is a suggestion that patients with elevated PSA levels treated to the pelvic lymph nodes (4,500 to 5,000 cGy), in addition to a boost to the prostatic bed (to a total dose of 6,500 cGy), have better results than patients treated to the prostatic bed only. However, longer follow-up is necessary to definitely ascertain the value of irradiation in these patients. Patients with postprostatectomy isolated, clincally palpable recurrences, when treated with irradiation (to 6,500 cGy), have a high probability of local tumor control (90% in 23 patients) at our institution. There is a suggestion that irradiation of the pelvic lymph nodes, in addition to the prostatic recurrence, yields better results. Unfortunately, approximately 60% of these patients develop distant metastases and have poor rates of survival. In conclusion, adjuvant irradiation plays a major role in patients treated with radical prostatectomy in various clinical situations. Radiation therapy as described is well-tolerated. Additional prospective randomized studies are necessary to better assess the role of irradiation in the treatment of these patients.

Journal Article↗

Pineal germinoma with unilateral blindness. Seeding of germinoma cells in optic nerve sheath.

A 13-year-old boy presented with blindness and loss of the papillomacular bundle in the left eye, bilateral papilledema sparing the area of axonal loss, and Parinaud's syndrome. Computerized tomography (CT) revealed an enlarged kinked left optic nerve and enlarged optic canal as well as a tumor in the pineal area producing hydrocephalus. Magnetic resonance (MR) scans showed multiple spinal metastases. The histological diagnosis was germinoma. On completion of four courses of chemotherapy with cis-platin, vinblastine, and bleomycin, repeated CT of orbita and MR imaging of the spine demonstrated the disappearance of the tumor surrounding the left optic nerve and of the spinal metastases. This is believed to be the first case report of seeding of germinoma into the perioptic arachnoid space.

Adolescent↗

Effect of differentiation-inducing agents on oncogene expression in a chronic myelogenous leukemia cell line.

K562 is a Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) blast crisis cell line representing a pluripotent precursor cell. At the molecular level, K562 cells express high levels of the aberrant bcr-abl product, p210bcr-abl, believed to be critical to the pathogenesis of CML. The authors demonstrate that exposure of K562 cells to hemin causes a state of partial, reversible erythroid maturation, accompanied by a marked decrease in p210bcr-abl. The change in bcr-abl expression may be mediated at the translational level since steady state amounts and enzymatic activity of the bcr-abl protein are reduced whereas bcr-abl mRNA levels are unaltered. The decrease in p210bcr-abl phosphokinase enzymatic activity can be detected within 2 hours after addition of hemin to the culture media, indicating that changes in expression of this oncogene probably occur before or concurrent with differentiation. No change in bcr-abl protein occurred in a CML cell line (KBM-5) which did not undergo differentiation after exposure to hemin, consistent with a direct relationship between altered p210bcr-abl expression and hemin-induced erythroid differentiation. Importantly, the marked diminution in bcr-abl protein was not associated with a disruption in K562 growth rates, indicating that the proliferative capacity of these cells may be independent of the bcr-abl product. In contrast to hemin, cytosine arabinoside (Ara-C) caused terminal erythroid differentiation of K562 cells, characterized by irreversible hemoglobin accumulation and cytostasis; and no change in bcr-abl protein expression was observed. The distinct effects of Ara-C and hemin could reflect the existence of pleiotropic differentiation pathways. Both Ara-C and hemin-exposed cells showed a decrease in c-myc and c-myb transcripts, suggesting that altered levels of these proto-oncogenes may be associated with erythroid maturation, regardless of the rate of cell division. K562 cells provide a useful model for analyzing the interaction between oncogene expression and CML cell growth and differentiation.

Cell Differentiation↗

Multiple restriction fragment length polymorphisms of the human epidermal growth factor receptor gene.

We have examined the epidermal growth factor (EGF) receptor gene for structural alterations in fresh human tumors. DNA samples from 92 patients with solid tumors (lung cancer, 37; breast cancer, 24; head and neck cancer, 17; other tumors, 14) were analyzed and compared with those from 22 leukemia patients and 14 individuals without malignant neoplasms. When DNA samples were digested with HindIII restriction endonuclease, Southern blot analysis demonstrated 3 distinct polymorphic bands (9.8, 11, and 12 kilobases) after hybridization to the HER-A64-1 probe and another 2 distinct polymorphic bands (4.9 and 5.2 kilobases) after hybridization to the HER-A64-3 probe. Pedigree analysis of 43 members of a single family and comparative analysis of tumor and normal DNA samples from the same patients demonstrated that the variations in fragment size observed were due to 2 independent restriction fragment length polymorphisms in the region of the EGF receptor gene. Amplification of the EGF receptor gene was detected in 3 cases of breast cancer, but not in other tumors studied. We conclude that the human EGF receptor gene has multiple restriction fragment length polymorphisms and that in fresh human tumor samples rearrangement and amplification of the gene occur infrequently, if ever, within the region encompassed by the 2 complementary DNA probes used.

Alleles↗

Analysis of the epidermal growth factor receptor gene in fresh human head and neck tumors.

Seventeen fresh uncultured tumors obtained from biopsies of patients with various forms of head and neck cancer and two squamous cell carcinoma cell lines were analyzed for RNA expression and structural alterations of the epidermal growth factor reception gene. We used cDNA probes for the external and the internal domains of the gene. Enhanced mRNA expression was found only in one squamous cell carcinoma cell line, which is known to have high levels of epidermal growth factor receptor. No amplification or structural rearrangement of the epidermal growth factor receptor gene was found.

Adenocarcinoma↗

Cytoplasmic inclusions and X-ray microprobe analysis in a case of prolymphocytic leukemia.

A patient with prolymphocytic leukemia is described. The peripheral blood and bone-marrow cells contained nuclear pockets, bridges, and appendices, as well as cytoplasmic inclusions that were not membrane bound or connected with the endoplasmic reticulum. X-ray microanalysis of the cells showed them to contain large amounts of phosphorus, sulfur, chlorine, and calcium, as well as a smaller amount of sodium and magnesium in comparison with control lymphocytes. When compared with lymphocytes of a patient with chronic lymphocytic leukemia (CLL), the patient's cells showed higher amounts of magnesium, sulfur, and chlorine, while the sodium content was decreased. The usefulness of electron microscopy and X-ray microanalysis in the diagnosis of this type of leukemia is discussed.

Adult↗

Transmission and scanning electron microscopy findings in 37 patients with monocytic leukemia.

The ultrastructural features of the monocytic blast cells of 37 patients with M4 and M5 types of leukemia were examined with transmission (TEM) and scanning (SEM) electron microscopes. The cells showed a large variety in nuclear size and shape, dependent on the stage of cell differentiation. Nuclear pockets, appendices and bridges were observed. The cytoplasm contained perinuclearly located fibrils, occasionally elongated mitochondria and Auer bodies. The surface ultrastructure of the cells was similar to that of healthy monocytes, but often numerous blebs were observed.

Adult↗

The influence of pre-radiation salivary flow rates and radiation dose on parotid salivary gland dysfunction in patients receiving radiotherapy for head and neck cancers.

Radiotherapy (RT) used for head and neck cancers causes permanent salivary gland dysfunction (SGD). Previous short-term studies have demonstrated that pre-RT salivary flow rates and the amount of radiation exposure to parotid glands influence the amount of RT-induced SGD. The purpose of this study was to determine which variables are related to the development of long-term post-RT SGD. Parotid flow rates (PFR) were assessed prior to and 1 year after completion of RT in spared parotid glands from 34 patients from 2 parotid-sparing protocols. The results reveal that spared PFR were not significantly higher 1 year post-RT in patients who had high pre-RT PFR, when compared with patients with low pre-RT PFR. However, patients who received higher doses of RT to spared parotid glands had lower PFR 1 year post-RT, compared with patients who had received lower doses of RT. These one-year findings suggest that high pre-RT PFR do not provide protection against RT-induced SGD. Conversely, reduced RT dosages to contralateral parotid glands are protective of PFR after completion of RT.

Adult↗