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Biomedical subjects

A K Raymond

Publications and source records attributed to A K Raymond.

At least 19 recordsLinked to original sources

Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid).

We have recently begun a phase II trial in patients with osteosarcoma who developed pulmonary metastases during adjuvant chemotherapy or who presented with pulmonary metastases that persisted despite chemotherapy. Eligible patients were rendered free of visible disease by surgery. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE, CGP 19835A lipid) (2 mg/m2) was infused twice weekly for 3 months. In five patients, a single tumor nodule recurred within 6 weeks after completion of therapy. These lesions were resected and submitted for pathological examination. Tissue specimens obtained after therapy were compared to those obtained before therapy. All the patients showed a histological change in the characteristics of the pulmonary tumors. In three patients, peripheral fibrosis surrounded the tumor and inflammatory cell infiltration and neovascularization were present. This is in contrast to central necrosis, with viable peripheral tumor cells and no inflammatory response observed in lesions resected following chemotherapy. In a fourth case, evidence of early fibrotic changes was found. This and the fifth case showed a change in malignant characteristics, from high grade before liposomal therapy to low grade after therapy. The present study provides evidence for a biological effect of liposomal MTP-PE.

Acetylmuramyl-Alanyl-Isoglutamine

Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum.

Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5-year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data.

Bone Neoplasms

Sclerosing adenosis of the prostate gland. A lesion showing myoepithelial differentiation.

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.

Acid Phosphatase

Amyloidosis in the upper aerodigestive tracts.

The upper aerodigestive tracts, particularly the larynx, are not uncommon repositories for amyloid. In most instances amyloidosis of the larynx is localized and is not associated with or followed by systemic disease. Oral and nasopharyngeal amyloidoses, on the other hand, are very often manifestations of systemic predisposing disorders. Laryngeal amyloidosis is treated, when indicated, by surgical removal, often repeated because of persistence or multifocal deposits.

Amyloidosis

Stensen's duct carcinomas.

Stensen's duct is rarely a primary site for a salivary neoplasm (11 examples in the English-language literature from 1927 to 1984). Bereft of myoepithelium, the neoplasms are histologically malignant and have been of mucoepidermoid, squamous, or undifferentiated types. Surgical management is predicated on the location and stage of the carcinoma.

Carcinoma

Surface osteosarcoma.

Osteosarcoma arising on the periosteal aspect of bone comprises a biologically heterogeneous group of neoplasms. The group as a whole may be referred to by a single descriptive term that emphasizes their common site of origin and underscores their malignant osteogenic potential: surface osteosarcoma. Its biologic heterogeneity may be approached via a number of avenues. Detailed description of individual tumors and grading are frequently employed. However, implementation of a classification system based upon reproducible clinical, roentgenographic, macroscopic, and histologic parameters is advantageous. The suggested classification system serves to clearly define parosteal and periosteal osteosarcoma, as well as recognize unusual variants. Most important, it defines therapeutic strategy. The classification system identifies low-grade, biologically indolent forms (i.e., parosteal osteosarcoma and periosteal osteosarcoma) that are best treated by surgery alone. At the same time, it recognizes high-grade forms with significant potential for life-threatening behavior (i.e., 'dedifferentiated' parosteal osteosarcoma and high-grade surface osteosarcoma) that are best managed by multimodality therapy incorporating chemotherapy and surgery.

Bone Neoplasms

Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group.

Sixty patients with extremity osteosarcoma were treated with intraarterial cisplatin. This was followed by surgical resection (amputation or limb salvage) and postoperative adjuvant chemotherapy utilizing two different protocols. Seventy-five percent of patients achieved an initial response. Overall disease-free survival was 58%. The number of patients treated with limb-salvage surgery gradually increased to the extent that 80% of newly-registered patients achieved a response and were subjected to limb salvage. Disease-free survival was 48% in amputation and 68% in limb salvage. The only factors found to have prognostic significance in determining disease-free survival were extent of tumor destruction induced by preoperative chemotherapy and tumor size.

Adolescent

Giant cell tumor of bone. A clinicopathologic and DNA flow cytometric analysis.

Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior.

Adult

Fine needle aspiration cytology of chondroblastoma of bone.

Between 1979 and 1987 12 patients with chondroblastoma underwent fine needle aspiration (FNA). There were eight female and four male patients (age range, 11-35 years) with lesions of the proximal humerus (three cases), distal femur (two cases), proximal tibia (two cases), proximal femur, distal tibia, talus, navicular bone, and fifth metacarpal (one case each). The radiologic features of the tumors were not entirely typical of chondroblastoma in the majority of patients. The aspirate was diagnosed as chondroblastoma in seven cases, was considered strongly suggestive of chondroblastoma in one case, was found to be diagnosable as chondroblastoma on review in one case, and was nondiagnostic in two cases. The remaining case, which showed giant cell tumor-like areas in addition to typical chondroblastoma on histologic sections from the curettage, was interpreted as giant cell tumor on FNA. There was no case in which an aspirate was erroneously diagnosed as chondroblastoma. On FNA, chondroblastoma had three dominant cytologic components: neoplastic mononuclear cells (chondroblasts), multinucleated osteoclast-like giant cells, and chondroid matrix fragments. The chondroblasts tended to lie individually in smears creating a pebbled appearance. They most commonly had round to oval nuclei with fine, evenly distributed chromatin and distinct longitudinal grooves, but indented, lobulated, and pyknotic nuclei were also observed. Their cytoplasm was dense and opaque with rounded well-defined borders. Multinucleated osteoclast-like giant cells were randomly admixed and were indistinguishable from those seen in other bone neoplasms. Chondroid matrix stained magenta with the Diff-Quik stain and green to violet with Papanicolaou. The cytologic features of the chondroblasts are the diagnostic hallmark of chondroblastoma and may allow FNA to become a valuable preoperative technique in the management of these patients.

Adolescent

Osteosarcoma: MR imaging after preoperative chemotherapy.

The authors reviewed 76 magnetic resonance (MR) images of 38 patients with osteosarcoma treated with preoperative chemotherapy (intraarterial cisplatin with or without systemic chemotherapy). Histologic maps of the surgical tumor specimens in 33 cases were correlated with either late-chemotherapy or postchemotherapy MR images. There were four MR patterns--dark, mottled or speckled, homogeneous, and cystic--that corresponded to different amounts of tumor matrix, granulation tissue, hemosiderin deposits, fluid-filled cysts, and residual viable tumor. Nested foci of residual viable tumor could not be specifically identified, although tumor progression or skip metastases were accurately depicted in four patients. Other findings included (a) peritumoral edema in the soft tissues and intramedullary space that shrank with chemotherapy, (b) chemotherapy effect in the surrounding soft tissues, (c) a dark rim around the extramedullary component of the tumors corresponding to a collagenous capsule continuous with the periosteum, (d) development of metaphyseal hemorrhages and bone marrow infarcts, and (e) intramedullary vascular channels.

Adolescent

Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience.

Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature.

Child

Small cell osteosarcoma. A clinicopathologic study of 27 cases.

We report a study of 27 patients with small cell osteosarcoma (SCO), 17 from the M. D. Anderson Cancer Center (MDAH) and ten from the Pediatric Oncology Group (POG). There were 12 male patients and 15 female patients; 19 were white, five were black, and three were Hispanic. They ranged from 6 to 28 years of age with a median of 14 years. Histologically there were three patterns: Ewing's-like, lymphoma-like, and spindle cell. All cases showed osteoid formation and a few had chondroid areas. There was cytoplasmic glycogen in ten cases. Initial treatment for MDAH patients included intraarterial infusion of cisplatin in ten, amputation in four, partial mandibulectomies in two, and biopsy with local radiotherapy and systemic chemotherapy in one. All POG patients had resection or amputation followed by adjuvant chemotherapy. Twelve patients are alive, of whom nine have had significant follow-ups for 25 to 90 months. Fourteen patients are dead of lung, spine, and brain metastases from 1 to 23 months after initial diagnosis. One patient is alive with lung relapse at 4 months. In summary, SCO is a high-grade variant of osteosarcoma, with an incidence of up to 4% of all osteosarcomas, that affects patients of the same age group and has the same anatomic location as conventional osteosarcoma. Currently, SCO appears to have a prognosis that is the same as or slightly worse than that of conventional osteosarcoma. Furthermore, although intraarterial infusion is effective for the primary tumors in the bone, distant metastases are difficult to control.

Adolescent

Effect of cumulative courses of intraarterial cis-diamminedichloroplatin-II on the primary tumor in osteosarcoma.

Preoperative chemotherapy with intraarterial cis-diamminedichloroplatin-II (CDP) and mannitol diuresis was administered to the primary tumor in 42 patients with osteosarcoma. The dose was 150 mg/m2 and more than 90% of the infusions were administered during a 2-week period. On occasion this period was extended to 3 weeks because of temporary renal insufficiency or logistical circumstances. Definitive surgical specimens were prepared by means of an arteriogram-directed plane of dissection with mapping and random sections. Histologically, tumor destruction was evaluated in terms of necrosis, inflammatory response, and fibrovascular regeneration. Quantification of the percent of tumor necrosis was as follows: less than 40% (consistent with spontaneous necrosis and/or no chemotherapy effect); 40% to 60% (possible chemotherapy effect); 60% to 90% (chemotherapy effect--partial response); and 90% to 100% (complete response). Therapeutic efficacy also was correlated with the number of CDP courses (one to three, four to five, and six to seven) and tumor subtype. Significant therapeutic effect (greater than 60% destruction) was observed with four or more CDP courses (one of nine tumors [one to three courses] versus 26 of 33 tumors [four to seven courses] [P = 0.01]). More than 60% of the tumor destruction was observed in the following subtypes: osteoblastic (22 of 28), fibroblastic (three of six), and telangiectatic (two of five). These data demonstrate that four or more courses of intraarterial CDP are required to achieve optimum effects and that osteoblastic osteosarcoma is highly responsive.

Cisplatin

Osteosarcoma: angiographic assessment of response to preoperative chemotherapy.

Adjuvant chemotherapy prolongs the survival of patients with high-grade osteosarcoma. Preoperative chemotherapy allows identification of effective agents for adjuvant chemotherapy based on response of the primary tumor. Preoperative determination of tumor response has therapeutic implications, and angiography offers a less subjective means of assessing it than do conventional radiography or computed tomography. Changes in tumor vascularity, as seen angiographically, after two courses and at the time of the last of several courses of preoperative chemotherapy were correlated with histologic tumor necrosis of resected specimens in 81 patients. Angiographically, 40% of the histologic responders and 91% of the nonresponders were identified after two courses of preoperative chemotherapy. After a median of four courses of chemotherapy, 91% of the responders but only 50% of the nonresponders were identified angiographically. Angiographic assessment of tumor vascularity, although not of absolute value, offers a useful guideline for determining the preoperative chemotherapy strategy.

Adult

Sialocysts of the parotid glands.

Sialocysts of salivary glands are outnumbered greatly by pseudocystic lesions, exemplified by mucoceles. In the major salivary glands, sialocysts are preponderantly lesions of the parotid glands, where they are classified as 1) salivary duct cysts, 2) lymphoepithelial cysts, or 3) dysgenetic or congenital cysts. All arise from salivary ducts and have no relation with the branchial apparatus.

Cysts