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Biomedical subjects

P D Savage

Publications and source records attributed to P D Savage.

At least 19 recordsLinked to original sources

Medical management of metastatic skeletal disease.

The medical management of metastatic disease generally includes chemotherapy, hormonal therapy, and metabolic pharmacologic manipulations with medications, such as bisphosphonates as well as nonoperative physical measures, such as orthoses and ambulatory or mobility aids. This comprehensive complex care is best coordinated with the medical oncologist. If well planned and coordinated, such care can improve the life of the cancer patient greatly.

Antineoplastic Agents↗

Low caloric expenditure in cardiac rehabilitation.

BACKGROUND: Total physical activity energy expenditure is a determinant of weight loss and risk factor modification in adults. There has been very little study of physical activity energy expenditure in cardiac rehabilitation populations. METHODS: Exercise-related energy expenditure was calculated in 112 patients with coronary artery disease in an outpatient cardiac rehabilitation program. Gross energy expenditure was estimated with the heart rate/oxygen consumption relation as measured during metabolic exercise testing with expired gas analysis. RESULTS: The average exercise training energy expenditure (ETEE) per cardiac rehabilitation exercise session was quite low at 270 +/- 112 kcal. Baseline fitness level (peak oxygen consumption), body weight, total exercise duration per session, age, and body mass index were all significant determinants of ETEE (r = 0.56 to -0.37, all P <.01). Additionally, patients who had undergone coronary bypass surgery and patients with medical comorbidities expended significantly fewer calories during exercise. In women, there was a relation between ETEE and change in total and LDL cholesterol (r = -0.43 and -0.45, respectively), although no such relation was observed in men. CONCLUSION: Cardiac rehabilitation exercise training, as currently structured, burns surprisingly few calories and has little impact in the short term (3 months) on measures of obesity and lipid risk factors. Alternative training programs should be considered to maximize caloric expenditure and modify specific risk factors such as obesity and dyslipidemia.

Aged↗

Is it necessary to biopsy the obvious?

OBJECTIVE: The radiologist and oncologist are often confident that biopsy will confirm their suspicion of recurrent disease, but a biopsy is performed to confirm the histologic diagnosis before beginning or altering therapy. We have examined data to determine how often the biopsied lesion represents recurrent disease from the primary tumor or is an instance of new cancer, and whether recurrent disease can be predicted. MATERIALS AND METHODS: We reviewed the medical and imaging records of 253 patients who underwent CT-guided biopsy of an abdominal or pelvic lesion between 1993 and 1996. Sixty-nine of the 253 patients had a previously diagnosed primary tumor and were being examined for possible tumor recurrence or metastasis. The images of these 69 patients were analyzed to determine if the pattern of disease was typical of recurrence or metastasis. RESULTS: In 55 of the 69 patients, the pattern was judged to be typical of metastatic or recurrent disease. Biopsy confirmed this suspicion in all 55 patients. In 14 of the 69 patients, the pattern of spread was judged not to be typical of recurrence or metastasis. These 14 patients were found to have a new primary tumor (n = 4), benign processes (n = 2), and recurrences (n = 8). CONCLUSION: Of the patients for whom radiographic findings suggested recurrence, we found no patients in whom a new primary tumor would have been missed if biopsy had been avoided. Data should now be acquired prospectively to determine whether it may be prudent to make treatment decisions on the basis of imaging findings alone, without histologic confirmation.

Abdominal Neoplasms↗

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

Adult↗

Fine-needle aspiration biopsy of skeletal versus extraskeletal osteosarcoma.

BACKGROUND: Although fine-needle aspiration biopsy (FNAB) of primary skeletal osteosarcoma (OS) has been described adequately, to the authors' knowledge, cytologic descriptions of extraskeletal OS appear limited to only rare case reports. METHODS: In an attempt to analyze the utility and accuracy of FNAB in a diagnosis of skeletal versus extraskeletal OS, the authors retrospectively reviewed their 5-year experience. The study sample included 15 skeletal OS specimens (13 primary, 1 local recurrence, and 1 pulmonary metastasis) in 14 patients ages 10-58 years (mean, 27 years; median, 25 years) and 5 extraskeletal OS specimens (3 primary and 2 metastatic) in 4 patients ages 36, 37, 65, and 79 years, respectively. Based on accepted clinical criteria, two patients (a mother with extraskeletal OS and a daughter with skeletal OS) had Li-Fraumeni syndrome. RESULTS: Of the adequate primary skeletal OS cases analyzed by FNAB, 10 of 12 (83%) were diagnosed correctly and subsequently treated according to a disease specific protocol. One case was considered unsatisfactory. One tumor initially was diagnosed as a giant cell tumor and another was referred to nonspecifically as "spindle-cell neoplasm." On histologic examination, the former case demonstrated a high grade fibroblastic OS arising within a giant cell tumor. None of the primary extraskeletal OS cases analyzed by FNAB was recognized as OS. One was diagnosed nonspecifically as "sarcoma" and the other was referred to simply as "atypical mesenchymal cells." A third case was comprised of scant fragments of adipose tissue, fibrous tissue, and cartilage and was considered unsatisfactory. Both examples of metastatic extraskeletal OS were recognized by FNAB. CONCLUSIONS: With appropriate clinicoradiologic correlation, skeletal OS generally is easily diagnosed by FNAB. Because of the older age of most patients with extraskeletal OS and the rather nonspecific radiographic findings (e.g., soft tissue mass), extraskeletal OS may not be recognized easily by FNAB and most likely requires incisional biopsy to establish a definitive diagnosis in most cases. Additional larger series will be required before drawing definite conclusions.

Adolescent↗

Fine-needle aspiration biopsy of synovial sarcoma. A cytomorphologic analysis of primary, recurrent, and metastatic tumors.

Thirteen fine-needle aspiration specimens from 10 patients with histologically proven synovial sarcoma are described. The aspiration biopsy specimens were obtained from the primary tumor in five cases, locally recurrent tumors in four cases, pulmonary metastases in three cases, and mediastinal metastasis in one case. Patient's ages ranged from 22 years to 65 years; there were four women and six men. All cases had a confirmation biopsy and/or resection specimen that were reviewed. Histologic subtypes included monophasic fibrous (5 cases), monophasic epithelial (1 case), biphasic (3 cases), and poorly differentiated (1 case). The majority of the aspiration biopsy specimens were similar with moderate to marked smear cellularity dominated by cohesive clusters of spindle-shaped cells with ovoid, hyperchromatic nuclei and scanty tapering cytoplasm. Nucleoli were not prominent. Epithelial tumor cells with ovoid to round, mostly regular, centrally to eccentrically located nuclei, surrounded by scant to abundant cytoplasm predominated in one case (monophasic epithelial) and were admixed with spindle cells in a second (classical biphasic). Multi-nucleated tumor giant cells were not observed in any of the tumors. In biphasic synovial sarcoma, the neoplastic spindle cells are generally more numerous and frequent than the epithelial cells, making distinction from monophasic synovial sarcoma or other spindle cell soft tissue tumors difficult. Although synovial sarcoma may be diagnosed by fine-needle aspiration cytology, clinical correlation, especially in monophasic types, is necessary to minimize errors in sarcoma classification.

Adult↗

Renal cell carcinoma.

Renal cell carcinoma remains a challenge to clinical medicine, with curative therapy experienced by a minority of patients. Mounting evidence suggests that the biological response modifiers, which consistently produce durable responses in some patients, may not need to be given in the high doses that have been associated with considerable, even fatal, toxicity; low-dose regimens in combination with conventional chemotherapeutic agents are yielding comparable, and possibly superior, results. Molecular biologic techniques have now advanced to the point where better classification schemes and prognostic variables are being elucidated, which may allow better optimization of specific treatment programs by allowing better patient discrimination. Further, with a better understanding of the molecular mechanisms of renal carcinogenesis, new agents and approaches to the problem of advanced renal cell carcinoma can be developed.

Carcinoma, Renal Cell↗

Renal cell carcinoma.

Renal cell carcinoma remains a devastating disease known for insidious onset, with patients often having advanced incurable disease at the time of diagnosis. Biologic therapy with IL-2 offers a chance for prolonged remission for a minority of patients, but its toxicities preclude most patients from ever receiving it. Preclinical experiments and early results of novel clinical trials based on the latest theories in molecular oncology and immunology are leading to promising new treatments for this disease.

Animals↗

Renal cell carcinoma.

Renal cell carcinoma remains a challenge for oncologists, with only 20% of patients being cured by surgical removal of the involved kidney and a handful of patients with advanced disease being cured by surgery, immunotherapy, or both. Although advances in early detection, recognition of high-risk groups, and chemotherapy remain disappointing, advances in immunotherapy as well as our basic understanding of the renal carcinoma cell have been made. Translation into clinical trials will likely occur within the next few years based on these findings.

Carcinoma, Renal Cell↗

Renal cell carcinoma.

The past year has been an exciting one for progress in our understanding of renal cell carcinoma. Substantial insight has been gained into our understanding of the immune system and how it both interacts with and is affected by renal cell carcinoma. The roles of the interferons and interleukins and the patients who are most likely to benefit from these agents have been better defined. Some new biologic markers of renal cell carcinoma have been described that may prove useful both prognostically and therapeutically. Lastly, advancement has been made in our basic understanding of the molecular aspects of renal cell carcinoma, which hold promise for better targeted, less toxic, and hopefully more effective treatment of patients with advanced disease.

Carcinoma, Renal Cell↗

Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints.

A probe identifying CBL2, the human cellular homolog of the murine oncogene v-cbl and murine cellular protooncogene Cbl-2, and panels of rodent X human somatic cell hybrids were used to study the relationship of this protooncogene to translocations associated with acute leukemia, lymphoma, and Ewing sarcoma. CBL2 was mapped to 11q23 and found to translocate from chromosome 11 to 4 in an acute leukemia cell line possessing a t(4;11)(q21;q23) and from chromosome 11 to 14 in a B-cell lymphoma with a t(11;14)(q23;q32). In an Ewing sarcoma cell line with a t(11;22)(q23;q12), however, CBL2 remained on chromosome 11. Additional studies of other genes in the region of 11q23 allowed the following ordering of these genes and breakpoints: 11cen--q23--NCAM--CD3(E-D-G)--[t(11;14), t(4;11)]--(THY1, CBL2, ETS1)--t(11;22)--11qter. The gross structure of the CBL2 sequences examined was not altered by either of the flanking breakpoints. Given that the 5' and 3' ends of the CBL2 gene are not known and are probably not evaluated by the v-cbl probe, these results do not rule out the possibility of CBL2 involvement in the pathogenesis of a subset of acute leukemias possessing a t(4;11), B-cell lymphomas possessing a t(11;14), or Ewing sarcomas possessing a t(11;22).

Animals↗

Tumefactive fibroinflammatory lesion of the extremity. Report of a case and review of the literature.

Tumefactive fibroinflammatory lesion is an idiopathic fibroinflammatory process of the head and neck region. Although benign histopathologically, it is invasive, destructive, and locally recurrent, leading to uncertainty regarding its proper management; as the disease is rare, determining optimal treatment is difficult, given the anecdotal nature of reports. We report the first case of a tumefactive fibroinflammatory lesion occurring outside the head and neck region. Our patient was treated with corticosteroids and had a favorable response, supporting this approach as initial treatment. Immunohistochemical studies performed on a pretreatment specimen were consistent with a secondary inflammatory component because no monoclonal nor aberrant phenotypes were detected. The tumefactive fibroinflammatory lesion appears to be indistinguishable from the other known idiopathic fibroinflammatory processes; patients presenting with any one of these should be evaluated for the others.

Adrenal Cortex Hormones↗

Poor prognosis of mediastinal germ cell cancers containing sarcomatous components.

Fifteen patients with biopsy-proven mediastinal germ cell tumors treated with platinum-based chemotherapy were reviewed. They had a period of 4 to 6 weeks between the onset of symptoms and diagnosis. Four patients had sarcomatous elements in their tumor in association with common germ cell histologies. The sarcomatous components consisted of one angiosarcoma, one rhabdomyosarcoma, and two cases with mixed angiosarcoma and rhabdomyosarcoma. All patients with sarcomatous elements died; the median survival for these patients was 9 months. In contrast, six (54%) of the patients who did not have sarcomatous elements in their tumor are long-term disease-free survivors 5 to 8 years after diagnosis. The occurrence of sarcomatous elements in a mediastinal germ cell tumor is a poor prognostic sign, and therapy should be oriented to include drugs and regimens that may be effective against sarcoma.

Adolescent↗

Mapping studies and expression of genes located on human chromosome 11, band q23.

Chromosome translocations and deletions may alter cellular proto-oncogenes and result in cellular changes that are important in the pathogenesis of malignancy. The region 11q23 is frequently involved in human malignancy. Utilizing a leukemic cell line with a reciprocal translocation involving 11q23 and somatic cell hybrids derived from this cell line, we analyzed five genes assigned to 11q23: NCAM, CD3D, CD3E, THY1, and ETS1. Our data showed no evidence of direct involvement of these genes in this leukemia but enabled a partial genetic map of this important region of the human genome to be constructed: 11cen--NCAM--CD3([G, D], E)--parallel--(ETS1, THY1)--11qter.

Animals↗

Identification of a restriction fragment length polymorphism involving the oncogene ETS-1 on chromosome 11q23.

Twenty four samples of DNA from 23 unrelated individuals were analyzed for the presence of a novel restriction fragment length polymorphism (RFLP) involving the proto-oncogene ETS-1 at an Xba I site. Four samples from unrelated individuals lacked an Xba I site, giving rise to a longer restriction fragment detectable by Southern analysis; two samples were from normal tissue, and two were from acute myelogenous leukemic blasts. Thus, no association could be found between the RFLP and disease among the individuals studied. Pedigree analysis of another cohort demonstrated Mendelian inheritance consistent with a somatic polymorphism. The practical applications of RFLP analysis in clinical and research settings, and the usefulness of this Xba I RFLP in the study of hematologic malignancies because of its location in 11q23, are discussed.

Acute Disease↗