Biomedical subjects

B Silver

Publications and source records attributed to B Silver.

At least 55 records · Page 3Linked to original sources

PubMed1998

Loss of cardiac magnesium in experimental heart failure prolongs and destabilizes repolarization in dogs.

OBJECTIVES: We sought to determine whether heart failure results in loss of cardiac magnesium sufficient to alter cellular electrophysiology. BACKGROUND: Free magnesium has numerous intracellular roles affecting metabolism, excitability and RNA synthesis. Total cardiac magnesium content is reduced in heart failure, but it is unclear whether magnesium loss is primary or iatrogenic. Furthermore, it is unknown whether free magnesium levels are affected or whether a change in free magnesium would alter cellular electrophysiology. METHODS: Eight mongrel dogs underwent demand ventricular pacing (VVI) at 250 beats/min for 3 weeks to induce heart failure. Sublingual epithelial magnesium was measured before pacing and at death. Left ventricular myocytes were isolated and loaded with Mag-Indo-1 to measure free magnesium ([Mg2+]i); myocytes from eight normal dogs served as controls. To test whether changes in [Mg2+]i in this range could alter cellular repolarization, current-clamped myocytes were dialyzed with 0.5 or 1.0 mmol/liter MgCl2. RESULTS: Mean sublingual epithelial magnesium fell significantly in the paced animals, from 36.9 +/- 0.5 to 33.9 +/- 0.7 mEq/liter (p < 0.01). Mean cardiac [Mg2+]i was significantly lower in the dogs with heart failure--0.49 +/- 0.06 versus 1.06 +/- 0.15 mmol/liter (p < 0.003). Time to 90% repolarization was significantly shorter in cells dialyzed with 1.0 mmol/liter compared with 0.5 mmol/liter MgCl2 in myocytes from normal dogs or dogs with heart failure (596 +/- 34 vs. 760 +/- 58 ms in normal dogs and 586 +/- 29 vs. 838 +/- 98 ms in dogs with heart failure; p < 0.05 for each). CONCLUSIONS: Experimental heart failure results in both tissue and cardiac magnesium loss in the absence of drug therapy. Free cardiac magnesium is significantly reduced, possibly contributing to abnormal repolarization in heart failure.

Action Potentials↗

PubMed1998

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation.

Our objectives were to measure and compare plasminogen activator inhibitor levels (PAI-1) in primary adult thrombotic thrombocytopenic purpura (TTP) and in secondary TTP associated with bone marrow transplantation (BMT)-TTP. PAI-1 antigen levels were measured by an enzyme linked immunosorbent assay on platelet poor plasma samples obtained from patients at the time of diagnosis of the TTP disorder and from a group of normal volunteers. The samples were frozen at -70 degrees C. Patients with TTP secondary to bone marrow transplantation had their grade determined by percentage fragmented cells and lactate dehydrogenase levels. The primary TTP samples were contributed by investigators in the multi-institutional North American TTP Group, and the bone marrow transplant samples were obtained from an adult bone marrow transplant program. Nineteen patients with adult TTP, and 47 patients with bone marrow transplant-TTP were evaluated. Of the latter, 14 had Grade 2, 13 had Grade 3, and 20 had Grade 4 BMT-TTP. PAI-1 levels were elevated compared to control volunteers in both primary adult TTP and BMT-TTP, P < 0.001. Levels did not differ from normal in Grade 2 BMT-TTP (median = 16 ng/ml; quartiles = 9-20). PAI-1 levels were similar in primary TTP (median = 32 ng/ml; quartiles = 25-51) and Grade 3 BMT-TTP (median = 35 ng/ml; quartiles = 19-48 ng/ml), P = 0.7. However, PAI-1 levels were significantly higher in Grade 4 BMT-TTP (median = 83 ng/ml; quartiles = 60-143) than Grade 3 BMT-TTP, and primary TTP, P < 0.001. PAI-1 levels are high in primary TTP and secondary bone marrow transplant-TTP (Grades 3-4). In contrast, normal levels are seen in Grade 2 BMT-TTP, which is a self-limited disorder. Therefore, high PAI-1 levels may contribute to hypofibrinolysis in the pathogenesis of primary TTP and of moderate to severe TTP (Grades 3-4) following bone marrow transplantation.

Adult↗

PubMed1998

Skin recurrences after breast-conserving therapy for early-stage breast cancer.

PURPOSE: To assess the frequency and prognosis of skin recurrences after breast-conserving therapy (BCT) compared with other breast recurrences. MATERIALS AND METHODS: From 1968 to 1986, 1,624 patients with unilateral stage I or II breast cancer treated with BCT at the Joint Center for Radiation Therapy (Boston, MA) underwent gross tumor excision and received a dose of > or = 60 Gy to the tumor bed. Skin recurrences (SR) were defined as breast recurrences without associated parenchymal disease. An invasive breast recurrence with any parenchymal disease noted clinically or radiographically was scored as an other breast recurrence (OBR). Median follow-up for survivors was 137 months. RESULTS: SR represented 8% (18 of 229) of all breast recurrences and occurred in 1.1% of all patients. The outcome after local recurrence was different for patients with SR and invasive OBR. Patients with SR more frequently had uncontrolled local failure (50%; 9 of 18) than did patients with OBR (14%; 26 of 188) (P = .0007). Forty-four percent (8 of 18) of patients with SR had distant metastasis simultaneously or within 2 months of the recurrence compared with 5% (9 of 188) of invasive OBR patients (P < .0001). For patients without distant metastasis at the time of recurrence, the 5-year actuarial rate of development of distant metastasis was 60% for SR patients compared with 39% for invasive OBR patients (P = .07), and the corresponding 5-year actuarial survival rates beyond the time of local failure were 51% and 79%, respectively (P = .06). CONCLUSION: In contrast to other types of invasive breast recurrence after breast-conserving therapy, skin recurrences are rare and are associated with a significantly higher rate of distant metastasis and uncontrolled local disease as well as a lower rate of survival.

Adult↗

PubMed1998

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer.

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.

Adult↗

PubMed1998

Predictors of breast recurrence after conservative surgery and radiation therapy for invasive breast cancer.

The majority of women with breast cancer are adequately treated with breast-conserving surgery and radiation therapy. Although most women need very limited surgery, some require a larger volume of resection to attain a high level of local control, and some might even require a mastectomy. This article summarizes the current state of knowledge concerning the assessment of the adequacy of excision.

Breast Neoplasms↗

PubMed1997

Treatment outcome after tangential radiation therapy without axillary dissection in patients with early-stage breast cancer and clinically negative axillary nodes.

PURPOSE: To determine the risk of nodal failure in patients with early-stage invasive breast cancer with clinically negative axillary lymph nodes treated with two-field tangential breast irradiation alone, without axillary lymph node dissection or use of a third nodal field. METHODS AND MATERIALS: Between 1988 and 1993, 986 evaluable women with clinical Stage I or II invasive breast cancer were treated with breast-conserving surgery and radiation therapy. Of these, 92 patients with clinically negative nodes received tangential breast irradiation (median dose, 45 Gy) followed by a boost, without axillary dissection. The median age was 69 years (range, 49-87). Eighty-three percent had T1 tumors. Fifty-three patients received tamoxifen, 1 received chemotherapy, and 2 patients received both. Median follow-up time for the 79 survivors was 50 months (range, 15-96). Three patients (3%) have been lost to follow-up after 20-32 months. RESULTS: No isolated regional nodal failures were identified. Two patients developed recurrence in the breast only (one of whom had a single positive axillary node found pathologically after mastectomy). One patient developed simultaneous local and distant failures, and six patients developed distant failures only. One patient developed a contralateral ductal carcinoma in situ, and two patients developed other cancers. CONCLUSION: Among a group of 92 patients with early-stage breast cancer (typically T1 and also typically elderly) treated with tangential breast irradiation alone without axillary dissection, with or without systemic therapy, there were no isolated axillary or supraclavicular regional failures. These results suggest that it is feasible to treat selected clinically node-negative patients with tangential fields alone. Prospective studies of this approach are warranted.

Aged↗

PubMed1997

Stage IA-IIB Hodgkin's disease: management and outcome of extensive thoracic involvement.

PURPOSE: To examine the presentation, management, and outcome of patients with extensive intrathoracic involvement in early-stage Hodgkin's disease. PATIENTS AND METHODS: One hundred seventy-two patients with clinical Stage IA-IIB Hodgkin's disease and extensive intrathoracic involvement were studied. Extensive intrathoracic disease was defined as either large mediastinal adenopathy (LMA, defined as the width of the mass greater than one-third the maximum thoracic diameter, n = 154) or as extensive (> 10 cm) cephalocaudad intrathoracic disease that did not fulfill formal chest radiograph criteria for LMA (n = 18). Patients were divided into three groups based on staging and extent of treatment. Forty-seven patients were treated with radiation alone after a laparotomy (RT-lap), 47 patients received combined modality therapy after laparotomy (CMT-lap), and 78 patients were treated with combined modality therapy without staging laparotomy (CMT-no lap). MOPP was used in 82% of the CMT patients. Low-dose whole-cardiac RT was used in nearly 50% of patients treated either with RT or CMT. RESULTS: The 10-year actuarial freedom from relapse rates were 54% with RT alone and 88% with CMT (p = 0.001); overall survival rates were 84 and 89%, respectively (p = NS). The median time to relapse was only 17 months. Over 80% of relapses occurred within the first 3 years. The most common site of relapse in all patients was the mediastinum. Relapses below the diaphragm were rare, even in CMT patients who did not receive abdominal radiation treatment. The principal acute morbidity was symptomatic pneumonitis, which occurred in 29% of patients receiving any part of their chemotherapy after RT, compared to 13% if all the chemotherapy was given before RT and 11% if RT alone was administered. There was a low late risk of myocardial infarction (3%) in the two groups with the longest follow up (RT-lap, CMT-lap), but a higher risk of second malignancy in the CMT-lap group (21%) compared with the RT-lap group (2%). CONCLUSION: Extensive intrathoracic involvement is a distinctive presentation of early-stage HD that has a high relapse risk if treated with RT alone. The introduction of CMT has been associated with improvements in freedom from relapse. The low rate of peripheral relapse with CMT suggests that reductions in field size may be achievable. The use of low-dose whole-heart RT with modern techniques is not associated with a high risk of late cardiac complications and should be used in patients who present with extensive pericardial disease or cardiophrenic lymphadenopathy. The high rate of second malignancy in the CMT group with the longest follow-up suggests that careful long-term surveillance for such patients is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Intracranial germinoma: the case for lower dose radiation therapy.

PURPOSE: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. METHODS AND MATERIALS: Between 1975 and 1995, 40 patients with the diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All patients received whole-brain (WB) RT (median dose: 32.4 Gy, range: 15-44.37 Gy) and a boost to the tumor volume (median total tumor volume dose: 52 Gy, range: 45-59.5 Gy). Thirty patients received RT to the spine (median dose: 26 Gy, range: 18.75-37.5 Gy). Four patients were treated with cisplatin-based chemotherapy and WB RT with a boost to the tumor volume (dose range: 51-54 Gy). A low-dose RT only group was defined as < or = 25.5 Gy to the WB (9 patients); < 50 Gy to the primary site (14 patients); and < 22 Gy to the spine (9 patients). Seventeen tumors were biopsy-proven germinoma, and 17 patients presented with multiple midline germinomas (MMG). Among 26 patients who had tumor markers measured, 27% had elevation of beta-human chorionic gonadotropin and by definition, no patient had an elevation of AFP. Twenty-four percent of 26 patients who had spine imaging or cerebral spinal fluid cytology had evidence of tumor seeding at diagnosis. The male to female ratio was 1.9:1. Median age at diagnosis was 14 years for male patients and 9.5 years for female patients (p = 0.02), (overall age ranges: 0.5-31 years). Median follow-up was 62 months (range: 3-226 months). Late effects of 29 patients with follow-up of > or = 20 months and adequate documentation in their medical records were analyzed. RESULTS: The 5-year actuarial rate of disease-free survival (DFS) and overall survival (OS) for biopsy-proven germinomas and presumed germinomas was 97%. No patient died of germinoma. There were no local failures regardless of the dose of RT, elevation of HCG tumor marker, or CSF dissemination at presentation. At presentation 22 patients had evidence of at least one endocrine abnormality. At follow-up there were no new patients diagnosed with an endocrine abnormality; however, 13 out of 22 patients had an increase in the number of endocrine deficiencies requiring hormone replacement. At presentation, 14 patients showed evidence of growth retardation. At follow-up there were no new cases of growth failure in the remaining patients. CONCLUSIONS: Germinomas are highly curable with RT alone. Lower doses of RT to the craniospinal axis without chemotherapy appear to produce equally effective DFS and OS as do higher doses of RT or combination chemotherapy and RT. Craniospinal RT may be indicated for patients with MMG or patients with evidence of spinal seeding. Long-term effects of growth retardation, and other endocrine deficiencies appear to be correlated with disease at presentation rather than solely with treatment.

Adolescent↗

PubMed1997

Is machine energy (4-8 MV) associated with outcome for stage I-II breast cancer patients?

PURPOSE: To assess the relationship between machine energy (4-8 MV) and treatment outcome in patients treated with conservative surgery and radiation therapy. METHODS AND MATERIALS: Between 1968 and 1985, 1624 patients were treated for clinical Stage I or II invasive breast cancer. The study population was limited to 1380 patients who underwent complete gross excision and received greater than or equal to 60 Gy to the tumor bed. Of these, 1125 were treated on a 4 MV, 153 on a 6 MV, and 102 on an 8 MV linear accelerator. Patients were selected for treatment on the 8 MV machine based on chest wall separations greater than 24 cm. Of patients treated on the 8 MV, netting was used for 42% and bolus was used for 26%. The median dose with bolus was 14 Gy in seven fractions (range: 2-34.2 Gy). Patients treated on the 8 MV accelerator were older, had a higher percentage of clinical T2 tumors, a higher percentage of pathologically positive nodes, and a lower incidence of extensive intraductal component (EIC). Median follow-up times were 130, 153, and 102 months, respectively, for survivors treated on the 4, 6, and 8 MV machines. RESULTS: We analyzed the site and 5-year crude incidence of first failure by machine energy and found the pattern of first failure site (local, nodal, or distant) to be virtually identical for each energy group. Of the local failures, 12 were in the skin of the treated breast, and these failures were evenly distributed by machine energy. We performed a multivariate analysis to adjust for factors known to predict for treatment failure. When adjusted for these other variables, machine energy was not associated with an increased (or decreased) risk of recurrence (RR for 8 MV vs. 4 MV = 0.94, p = 0.7; RR for 6 MV vs. 4 MV = 1.0, p = 0.9). We also analyzed the nature and incidence of treatment complications (rib fracture, radiation pneumonitis, soft tissue necrosis, and brachial plexopathy) and found no significant differences among the three treatment groups when stratified by treatment technique (tangents only vs. three-field). There was also no significant difference in cosmetic outcome at 5 years among the three groups. CONCLUSIONS: We conclude that machine energy over the range of 4 to 8 MV does not significantly affect treatment outcome. Specifically, it was feasible to treat patients with large chest wall separations using an 8 MV machine without an increase in skin recurrences and with the improved dose homogeneity afforded by 8 MV machines as compared with those of lower energies.

Adult↗

PubMed1997

Fulminating encephalopathy with perivenular demyelination and vacuolar myelopathy as the initial presentation of human immunodeficiency virus infection.

OBJECTIVE: To study the neuropathologic features in a case involving a 22-year-old woman in whom a fulminating encephalopathy developed as the initial manifestation of human immunodeficiency virus (HIV) infection. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: The patient presented with rapidly progressive mental status, changes, cranial nerve abnormalities, and quadriplegia, which led to her death 5 months later. Serologic tests for HIV were initially indeterminate on Western blot analysis but were positive 1 week later. METHODS: A complete autopsy, including examination of the brain and spinal cord, was performed. Paraffin-embedded sections of the brain and spinal cord were examined using standard histologic staining procedures and immunohistochemical techniques. RESULTS: Neuropathologic examination revealed discrete foci of perivenular demyelination disseminated throughout the brain and spinal cord, as well as severe vacuolar myelopathy. Lesions typical of HIV encephalitis were not present. Human immunodeficiency virus-infected monocytes and microglia were observed in the vicinity of, but not restricted to, the perivenular demyelinating lesions. No other infectious agents were identified. CONCLUSIONS: The patient's acute encephalopathy was most likely the direct result of a widespread demyelinating process resembling acute disseminated encephalomyelitis. We suggest that the perivenular demyelination may represent an autoimmune reaction, possibly due to a nonspecific viral infection, occurring in the setting of chronic immunosuppression secondary to HIV. Although less likely, we cannot exclude the possibility that HIV could have directly triggered an autoimmune response that caused the acute disseminated encephalomyelitis-like lesions.

Adult↗

PubMed1997

Childhood soft tissue sarcoma: a 20-year experience.

PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.

Adolescent↗

PubMed1997

Evaluating GPAs and MCAT scores as predictors of NBME I and clerkship performances based on students' data from one undergraduate institution.

PURPOSE: To examine the relationships among undergraduate student characteristics, standardized indicators of medical school academic performance, and clinical performances in an institution where the undergraduate grading system was not a confounding factor. METHOD: In 1993 data were collected retrospectively for the classes of 1990-1993 in the University of California, Riverside (UCR)/University of California, Los Angeles, Biomedical Sciences Program, in which all the students completed their undergraduate studies at UCR. Data were collected on the students' demographic characteristics, undergraduate grade-point averages (UGPAs), Medical College Admission Test (MCAT) scores, National Board of Medical Examiners Part I (NBME I) scores, and clinical performances as measured by core clerkship grades. Regression analyses were used to evaluate (1) the relationship between clinical performances and data available at admission and (2) the relationship between NBME I scores and the same variables. The top and bottom 25% of each class were identified by UGPAs and compared by their NBME I scores and clinical performances to determine whether differences noted at admission continued to separate the students. Differences were tested using independent two-tailed t-tests. RESULTS: Of the 92 students, data were available for 88 (96%); 39% were female and 38% were foreign-born. The sample was fairly heterogeneous in terms of UGPAs, MCAT scores, clinical performance grades, and NBME I scores. Results of the first regression analysis indicated that mean clinical performance was not related to any of the undergraduate predictors of performance or to the students' demographics. The second regression analysis indicated that MCAT scores and cumulative science UGPAs were related to performance on the NBME I, as were country of origin and sex. The students in the top and bottom 25% differed significantly in their scores on the NBME I, but not in their clinical performances. CONCLUSION: Although UGPAs and MCAT scores are good indicators of NBME I performance, they are still not useful in predicting clinical performance, even when the students' data are taken from the same undergraduate institution.

California↗

PubMed1997

Tissue magnesium levels and the arrhythmic substrate in humans.

INTRODUCTION: Magnesium deficiency has been implicated in the pathogenesis of sudden death, but the investigation of arrhythmic mechanisms has been hindered by difficulties in measuring cellular tissue magnesium stores. METHODS AND RESULTS: To see if magnesium deficiency is associated with a propensity toward triggered arrhythmias, we measured tissue magnesium levels and QT interval dispersion (as an index of repolarization dispersion) in 40 patients with arrhythmic complaints. Magnesium was measured in sublingual epithelium using X-ray dispersive analysis. QT interval dispersion was assessed on 12-lead surface ECGs in all patients, and programmed stimulation was performed in 28. The sublingual epithelial magnesium level ([Mg]1), but the not the serum level, correlated inversely with QT interval dispersion in 40 patients (r = 0.58, P < 0.005); in 12 patients undergoing repeat testing on therapy, the change in magnesium also correlated inversely with the change in QT dispersion (r = 0.61, P < 0.05). Patients with left ventricular ejection fractions > 40% had significantly higher tissue magnesium and lower QT dispersion (34.5 +/- 0.5 mEq/L, 81 +/- 8 msec) than those with left ventricular ejection fractions < 40% (32.7 +/- 0.5 mEq/L, P < 0.01, and 114 +/- 9 msec, P < 0.05). There was no difference in either [Mg]1 or QT dispersion in the 16 patients with inducible monomorphic ventricular tachycardia versus the 12 noninducible patients. CONCLUSION: Reduced tissue magnesium stores may represent a significant risk factor for arrhythmias associated with abnormal repolarization, particularly in patients with poor left ventricular systolic function, but may not represent a risk for excitable gap arrhythmias associated with a fixed anatomic substrate (e.g., monomorphic ventricular tachycardia).

Adult↗

PubMed1997

Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease.

PURPOSE: The patterns of presentation, histologic pattern (nodular or diffuse), treatment, and long-term outcome were studied in patients with lymphocyte-predominant (LP) Hodgkin's disease (HD) to determine whether these patients should be treated differently than patients with other subtypes of HD. PATIENTS AND METHODS: Pathology was reviewed for 97 patients with an initial diagnosis of LPHD made between 1970 and 1993. Seventy-five patients had LPHD on review: 55 had nodular LPHD, 14 had diffuse LPHD, and six had LP histology without subclassification. There were 60 males (80%) and 15 females (20%). Sixty-six patients (88%), presented with clinical stage (CS) I or II disease. Seventy-one patients were treated at the Joint Center for Radiation Therapy (JCRT) and were considered for analysis of treatment outcome. Sixty-one of these 71 were treated with radiation (RT) alone; 17 received mantle RT alone, 27 mantle and paraaortic RT, and seven total-nodal irradiation (TNI). Ten patients with subdiaphragmatic HD received pelvic and paraaortic RT. Of the 10 remaining patients, four were treated with RT and chemotherapy (CT) and six were treated with CT alone. The median follow-up time was 10.8 years. RESULTS: The 10-year actuarial freedom-from-first-relapse (FFR) and 10-year overall survival rates for the 71 patients with LPHD treated at the JCRT were 80% and 93%, respectively. The 10-year actuarial FFR by nodular (n = 51), diffuse (n = 14), and unspecified (n = 6) histologic pattern was 74%, 100%, and 60%, respectively. Overall, 14 of 71 patients have relapsed: nine of 61 with stage IA, IB, or IIA disease and five of 10 with stage IIB to IVB disease have relapsed. The median time to relapse was 53 months. Nine of 71 patients have died. Only one death has been from HD: five patients died of second cancers, two of cardiac disease, and one of alcoholic liver cirrhosis. Of seven patients with second malignancies, five died. None of the second malignancies were non-Hodgkin's lymphoma (NHL). CONCLUSION: Patients with LPHD have different patterns of presentation, sex and age distribution, and likelihood of occult abdominal disease than patients with nodular-sclerosing (NS) or mixed-cellularity (MC) disease. The median time to relapse for LP patients was later than reported for other histologic subtypes; however, there was no pattern of continuous late relapse. With pathologic staging and standard treatment, mortality from LPHD is low; nearly all deaths have been cardiac- or second tumor-related. This suggests that less aggressive treatment for LPHD might continue to yield excellent results, while perhaps lowering the long-term risk of complications.

Adolescent↗

PubMed1997

Experimental arteriovenous fistulas: treatment with silicone-covered metallic stents.

PURPOSE: To determine the efficacy of silicone-covered metallic stents in the treatment of experimentally created carotid-jugular fistulas. METHODS: Carotid-jugular fistulas were surgically constructed in six mongrel dogs. Silicone-coated, self-expanding metallic stents were placed across the fistula holes within the carotid artery, and carotid angiography was performed before, immediately after, and 4 and 8 weeks after stent placement. Fistula specimens were resected 2 months after stent placement and analyzed by means of gross and light microscopy. RESULTS: Angiography revealed complete closure of all fistulas immediately after stent deployment. The fistulas remained closed and all carotid arteries remained patent. Marked stenosis within the carotid lumen was seen along the proximal and distal ends of the stents. Gross and micropathologic specimens of the carotid-jugular fistulas revealed fibrous connective tissue and collagen across the fistula holes. Proliferative fibrous connective tissue, collagen, and fibromyoblasts were located at either end of the stents. The wires of the stents indented the intraluminal surface of the carotid arteries. CONCLUSIONS: Silicone-covered stents were effective in closing all experimentally created carotid-jugular fistulas. With further refinements and variations in technique, covered stents may prove a viable alternative to current endovascular devices.

Animals↗

PubMed1996

Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy.

BACKGROUND: The relationship between the microscopic margins of resection and ipsilateral breast recurrence (IBR) after breast-conserving therapy for carcinomas with or without an extensive intraductal component (EIC) has not been adequately defined. METHODS: Of 1,790 women with unilateral clinical Stage I or II breast carcinoma treated with radiation therapy as part of breast-conserving therapy, 343 had invasive ductal histology evaluable for an extensive intraductal component (EIC), had inked margins that were evaluable for an review of their pathology slides, and received > or = 60 Gray to the tumor bed; these 343 women constitute the study population. The median follow-up was 109 months. All available slides were reviewed by one of the study pathologists. Final inked margins of excision were classified as negative > 1 mm (no invasive or in situ ductal carcinoma within 1 mm of the inked margin); negative-1 mm, or close carcinoma < or = 1 mm from the inked margin but not at the margin); or positive (carcinoma at the inked margin). A focally positive margin was defined as invasive or in situ ductal carcinoma at the margin in three or fewer low-power fields. The first site of recurrent disease was classified as either ipsilateral breast recurrence (IBR) or distant metastasis/regional lymph node failure. RESULTS: Crude rates for the first site of recurrence were calculated first for all 340 patients evaluable at 5 years, then separately for the 272 patients with EIC-negative cancers and the 68 patients with EIC-positive cancers. The 5-year rate of IBR for all patients with negative margins was 2%; and for all patients with positive margins, the rate was 16%. Among patients with negative margins, the 5-year rate of IBR was 2% for all patients with close margins (negative < or = 1 mm) and 3% for those with negative > 1 mm margins. For patients with close margins, the rates were 2% and 0% for EIC-negative and EIC-positive tumors, respectively; the corresponding rates for patients with negative margins > 1 mm were 1% and 14%. The 5-year rate of IBR for patients with focally positive margins was 9% (9% for EIC-negative and 7% for EIC-positive patients). The 5-year crude rate of IBR for patients with greater than focally positive margins was 28% (19% for EIC-negative and 42% for EIC-positive patients). CONCLUSIONS: Patients with negative margins of excision have a low rate of recurrence in the treated breast, whether the margin is > 1 mm or < or = 1 mm and whether the carcinoma is EIC-negative or EIC-positive. Among patients with positive margins, those with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins, and could be considered for breast-conserving therapy.

Breast Neoplasms↗

PubMed1996

Relationship of tumor grade to other pathologic features and to treatment outcome of patients with early stage breast carcinoma treated with breast-conserving therapy.

BACKGROUND: Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS: The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS: High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (p = 0.002). CONCLUSIONS: Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management.

Breast Neoplasms↗

PubMed1996

The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.

BACKGROUND: Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear. METHODS: Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12-week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124). RESULTS: The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy-first group and the chemotherapy-first group were 38 percent and 31 percent (P = 0.17) and 36 percent and 25 percent (P = 0.05), respectively. Overall survival was 73 percent and 81 percent (P = 0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both. This difference in the pattern of recurrence was of borderline statistical significance (P = 0.07). CONCLUSIONS: This study suggests that for patients ar substantial risk for systemic metastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy.

Actuarial Analysis↗