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R A Goldschmidt

Publications and source records attributed to R A Goldschmidt.

18 recordsLinked to original sources
PubMed1999

Sentinel lymphadenectomy for breast cancer: experience with 180 consecutive patients: efficacy of filtered technetium 99m sulphur colloid with overnight migration time.

BACKGROUND: Axillary node status remains the most important prognostic indicator of survival in breast cancer patients. Only 25% to 35% of patients having standard level I/II axillary dissection have involved nodes, yet all accept the potential for morbidity after the operation. This study was conducted to assess whether status of the sentinel node(s) was an accurate predictor of the presence of metastatic disease in axillary or internal mammary nodes. STUDY DESIGN: In 180 patients, technetium 99m sulphur colloid was injected in a 4-quadrant peritumoral distribution. During the first phase of the study, 72 patients had sentinel node excision followed by a level I/II axillary dissection. During the second phase of the study, 108 patients had sentinel node excision and only those with positive nodes had completion axillary dissection. Nodes were examined after formalin fixation by taking 10 sections at 20-microm intervals and staining with hematoxylin-eosin. RESULTS: Sentinel nodes were found in 162 (90%) of 180 patients. The mean number of sentinel nodes examined was 3.1. Of the 162 patients with successful lymphatic mapping, positive sentinel nodes were found in 44 (27%). In 23 (66%) of 35 patients with positive sentinel nodes who had a completion level I/II axillary dissection, the sentinel nodes were the only positive nodes. The concurrent negative predictive value was 4% in the first 72 patients who had completion axillary dissection after sentinel node excision, and 2% for the entire series. With evolution of technique, identification of sentinel nodes with radiolabeled colloid was successful in 97% of the last 100 patients. CONCLUSIONS: Because the concurrent negative predictive value was low, sentinel node excision appeared to accurately identify node status, potentially avoiding the need for standard level I/II axillary dissection in sentinel node-negative patients.

Axilla↗
PubMed1995

Growth and metastasis of human breast cancers in athymic nude mice.

To evaluate critically the merit of utilizing a wound model for growing human tumors, a series of increasingly difficult human tumor types were tested for growth at sites of trauma in athymic nude mice. In vitro tumor lines as well as fresh tumors from the breast, colon, rectum, lung, and a metastasis from an unknown primary were intraperitoneally injected into mice subjected to intra-abdominal organ injury. Successful xenografts were obtained from nine of 10 cell lines and 14 of 24 fresh tumors. The latter included five of six (83%) colon cancers, one lung tumor, metastatic tumor of unknown primary, three of four (75%) metastatic breast cancers and four of six (67%) estrogen receptor (ER)-negative breast primary tumors. Six ER-positive breast tumors tested failed to grow in mice without estrogen supplementation. Xenografts from two breast, two colon and the lung cancers formed spontaneous metastases and all xenografts tested were able to yield serial transplants in the surgical wound model. Histologically, all xenografts and their metastases were identical to their respective donor tumors. Transplantability in mice without exogenous estrogen supplementation was linked to the absence of estrogen and progesterone receptors in breast tumors. Transplantability of the cell lines was associated with the expression of cell surface receptors for fibronectin and hyaluronic acid. Receptors for other extracellular matrix components, namely, laminin, vitronectin, collagen, fibrinogen or von Willebrand factor were not associated with transplantability. These results demonstrate that a large proportion of human tumors, including the breast tumors, can be successfully xenografted into athymic mice by providing them with a healing wound environment, and that such xenografts grown at ectopic sites exhibit metastatic ability.

Animals↗
PubMed1995

Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.

Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.

Animals↗
PubMed1993

DNA flow cytometry and pathologic grading as prognostic guides in axillary lymph node-negative breast cancer.

BACKGROUND: The recurrence or mortality rate of axillary lymph node-negative invasive breast cancer has been associated with the tumor S-phase fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using frozen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. METHODS: Histologic, nuclear, and mitotic grades, DNA ploidy, and S-phase fraction (SPF) were determined from paraffin-embedded tumors obtained from 280 women with node-negative invasive ductal carcinomas using standard grading schemes and flow cytometric techniques. These variables were compared with disease-free and cancer-specific survival (CSS) in univariate and multivariate analyses of these patients. RESULTS: Tumor diameter, SPF, histologic grade, and nuclear grade were significant predictors of disease-free survival (DFS); diameter and SPF had significant associations with CSS. Cox analysis showed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% risk of recurrence at 5 years. In contrast, 36% of patients in this series with medium-grade or high-grade high SPF tumors had a 30% risk of recurrence over the same interval. CONCLUSIONS: Histopathologic grading and flow cytometric determination of SPF appear to provide additive prognostic information for patients with early invasive ductal carcinomas of the breast.

Aneuploidy↗
PubMed1993

The role of fibronectin in tumor implantation at surgical sites.

Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre-exposed to 200 micrograms/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer.

Adenocarcinoma↗
PubMed1991

Inhibition of tumor implantation at sites of trauma by plasminogen activators.

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.

Adenocarcinoma↗
PubMed1990

Improved detection of metastases to lymph nodes and estrogen receptor determination.

We present a new method for detection of micrometastases to axillary lymph nodes and estrogen receptor determination. Cellular suspensions from primary infiltrating ductal breast carcinoma or level I axillary lymph nodes of patients who underwent mastectomies were obtained, by loosely grinding fresh tumors or lymph nodes through a grid and then transferring the matrix to a slide using cytocentrifugation. Tumor samples were analyzed for estrogen receptor status using an immunocytochemical kit and compared with the dextran-coated charcoal method. Thirty-eight of 48 correlated (20 were estrogen positive, and 18 were estrogen negative). Seven of 46 were estrogen positive while results from the dextran-coated charcoal method were estrogen negative. One of 46 was estrogen negative, while the results from the dextran-coated charcoal method were estrogen positive. Lymph node slide preparations were stained to detect tumor cells using antikeratin monoclonal antibodies. Three of 8 node-negative patients were found to have micrometastases. Four of 15 node-positive patients had additional nodes with tumor. Our method combines the advantages of serial sectioning and immunohistochemical staining.

Antibodies, Monoclonal↗
PubMed1990

The importance of DNA flow cytometry in node-negative breast cancer.

DNA flow cytometric analysis and conventional clinical factors were compared with disease outcome in 257 patients with node-negative infiltrating ductal carcinoma who had been treated between 1976 and 1983. Median follow-up was 80 months; none of the patients received adjuvant therapy. The relative prognostic importance of clinical variables, ploidy, and S-phase fraction was analyzed by Cox multivariate analysis. Ploidy was analyzable for 198 tumors and did not predict survival. Nuclear grade predicted disease-free survival for all patients. For 71 patients with diploid tumors, only high S-phase had a statistically significant association with relapse. For 127 patients with aneuploid tumors, tumor diameter predicted both disease-free survival and cancer death; histologic grade was also significant for predicting disease-free survival. In conclusion, flow cytometric determination of ploidy and S-phase fraction can provide valuable predictive information in node-negative breast cancer in addition to conventional variables.

Breast Neoplasms↗
PubMed1989

The influence of surgical trauma on experimental metastasis.

Influence of surgical trauma on experimental metastasis in healing wounds is investigated using a transplantable murine mammary carcinoma cell line, TA3Ha. Intravenous injection of 10(5), 10(6), and 2 x 10(6) TA3Ha cells into syngeneic Strain A mice led to liver or kidney tumor development in none of the 96, ten, and ten mice tested, respectively. In contrast, injection of 10(5) cells into mice immediately after hepatic wedge resection performed using milliwatt carbon dioxide laser and electrocautery resulted in tumor formation at the site of trauma in 21/37 (57%) and 25/52 (48%) mice, (P less than 0.001) respectively. Similar results were obtained in mice subjected to partial nephrectomy using the laser (nine of 18) and electrocautery (eight of 13). These results clearly demonstrate that surgical trauma renders a nonprivileged organ susceptible to experimental metastasis formation, and that at least in this model both laser and electrocautery have similar effects. Tumor cell injection 1, 7, and 10 days posthepatic surgery resulted in 36%, 20%, and 0% tumor formation, respectively, indicating that the earlier events in wound healing support tumor implantation and/or growth better than those later on. Frequency of tumor formation at sites of trauma in the peritoneum induced by scalpel blade, laser, and electrocautery were 28%, 50% and 82%, respectively. Peritoneal tumors were seen in 33% of the nonsurgical mice. Skin incisions induced with the three above probes had little influence on experimental metastasis formation. Thus the influence of trauma on tumor formation is not uniform in every organ.

Animals↗
PubMed1989

Partial nephrectomy in mice with milliwatt carbon dioxide laser and its influence on experimental metastasis.

We have developed a surgical model to perform partial nephrectomy in mice using the milliwatt CO2 laser and have used this model for studying the influence of the sequel of surgery on experimental tumor metastasis. Strain A mice were subjected to partial nephrectomy using the milliwatt CO2 laser. The surgical procedure was time efficient, the blood loss was minimal, and the postoperative mortality was 6%. Immediately after surgery, the wound consisted of a superficial layer of charring and a deeper layer of thermal damage (coagulative necrosis). The wound healing was completed within 30 days and was accompanied by fibroblast infiltration and tubular regeneration but minimal inflammatory response. Seventy surgical mice were injected I.V. with TA3Ha murine mammary adenocarcinoma cells at different intervals (immediately to 30 days) after surgery. Among 38 mice inoculated with tumor cells immediately or up to 3 days after surgery, 18 (47%) showed histologically confirmed tumors at the site of surgical trauma. None of the 38 unoperated kidneys showed any evidence of tumor. This difference is statistically significant at a P value of less than 0.001. As the interval between surgery and tumor inoculation was increased to 7, 15, and 30 days, the frequency of tumor formation at the site of surgery decreased to 20% (2/10), 14% (2/14), and 0% (0/8), respectively. The results demonstrate that a) partial nephrectomy in mice is feasible with minimal mortality or apparent morbidity, b) the laser-induced surgical trauma favors implantation and growth of tumors, c) the frequency of tumor formation is related to the stage of wound healing, and d) the tumors are anatomically related to the healing wound but do not invade into the parenchymal tissue.

Adenocarcinoma↗
PubMed1988

Lymph node infarction and malignant lymphoma: a case report.

An infarcted lymph node can precede, or occur simultaneously with, malignant lymphoma. Not infrequently a pathologic diagnosis of necrotic lymph node leaves the clinician puzzled as to its etiology after infectious and traumatic causes are excluded. The head and neck surgeon should be aware of this association and be prepared to follow these patients closely or rebiopsy to prevent delayed diagnosis of a malignant lymphoma. The literature is reviewed and a case of lymph node infarction with malignant lymphoma is presented to illustrate this clinicopathologic correlation.

Humans↗
PubMed1986

Milliwatt carbon dioxide laser and hepatic surgery in mice: surgical technique and pathology.

The milliwatt carbon dioxide laser was used to induce focal lesions and to perform wedge resections in the livers of 75 strain A mice. The procedures were feasible and well tolerated by the mice, with only one postoperative death in the wedge resection group in an early experiment. The hepatic lesions produced by the laser were characterized histologically by an inner area of vaporization, an intermediate area of coagulation necrosis, and an outer rim of cells with variable damage. The lesions healed by fibroblastic proliferation and scar formation with no hepatocytic contribution. The small vessel and bile ductule sealing effect of CO2 laser, together with the sound healing of laser-induced wounds, highlights the usefulness of this modality in liver surgery in general, and suggests its particular application in the treatment of liver trauma and a variety of hepatic focal lesions, neoplastic or otherwise.

Animals↗
PubMed1984

Computed tomography versus angiography in the diagnosis of large right adrenal carcinomas.

Adrenal carcinomas are rare. We present four surgically and pathologically proved large right adrenal carcinomas studied by computed tomography, angiography, and other imaging modalities. Computed tomography demonstrated large nonhomogeneous right upper quadrant masses in all four cases, but the adrenal origin of the mass could not be ascertained by computed tomography in three patients due to the transverse display of the anatomy. Ultrasonography provided important additional information in these cases. Arteriography was diagnostic in each case by demonstrating minimal to marked tumor vascularity supplied by adrenal arteries. We also present, for differential diagnostic purposes, a proved benign adrenal hemorrhagic cyst with computed tomography and angiography findings indistinguishable from those of adrenal carcinomas. Computed tomography does not eliminate the need for angiography in patients with large right upper quadrant masses suspected of being an adrenal carcinoma.

Adrenal Gland Diseases↗
PubMed1982

Infantile sarcoma with intracytoplasmic filamentous inclusions: distinctive tumor of possible histiocytic origin.

This report describes four malignant tumors originating in infants, (one present at birth), for which a common origin is proposed. The common nature of these tumors was suggested by a remarkable similarity of histologic and ultrastructural features, including the presence of intracellular filamentous aggregates, as well as a shared aggressive clinical course consistent with sarcomatous origin. Two of these neoplasms arose within the kidney and were classified as "rhabdoid" sarcomas, according to the NWTS nomenclature. However, cells from these neoplasms could not be identified as muscular in origin. In culture, these cells demonstrated adherence to substratum, ability to phagocytose particles, and cell surface complement receptors. In addition, the renal tumors contained definite tumor cells positive for muramidase; the liver primary tumor contained only a limited number of such cells, which could not be interpreted as neoplastic. These findings suggest that among the "round-cell sarcomas" of infants and young children, a distinct, highly malignant form may be identified on clinical and morphologic grounds. The possibility that the tumor cells may be linked to the mononuclear phagocyte system was suggested, but not proved, and deserves further study.

Female↗
PubMedDate not supplied

Lobular carcinoma in situ of the breast.

Lobular carcinoma in situ (LCIS) of the breast is commonly identified as an incidental finding in breast biopsies performed because of either a mammographic abnormality or a palpable mass. Although long recognized as an entity, the significance and optimal treatment of LCIS remains controversial. Initially regarded as a pre-invasive form of breast cancer analogous to ductal carcinoma in situ (DCIS), LCIS was treated by mastectomy. As evidence mounted for an equal risk of invasive carcinoma in both breasts, bilateral mastectomy was advocated by some. More recent studies suggest that LCIS is a marker for increased risk rather than a true precursor of invasive carcinoma, and this allows a more conservative approach. The pathologic aspects and natural history of LCIS are discussed.

Biopsy↗
PubMedDate not supplied

The diagnosis and management of ductal carcinoma in-situ of the breast.

The widespread utilization of screening mammography has produced a shift in the stage of breast cancer at diagnosis in the US: Currently, 12% to 15% of newly diagnosed breast cancer cases annually are ductal carcinoma in-situ (DCIS). The diagnosis is made, in at least 90% of patients, with mammography. Only about 10% of patients will have a palpable mass. The accurate characterization and visualization of calcifications typically requires magnification of mammographic imaging. The morphology of the calcifications is generally considered to be the most important factor in differentiating benign from malignant formations. Round and uniform shapes are more likely to be benign, while linear and heterogeneous morphologies are associated with DCIS. Following a complete mammographic work-up, most suspicious lesions are potential candidates for a stereotactic core needle biopsy. Ten percent to 50% of patients initially diagnosed with atypical ductal hyperplasia by needle biopsy have subsequently been surgically diagnosed with cancer near the biopsy site. Due to this relatively high incidence of co-existent carcinoma, a needle biopsy diagnosis of atypical ductal hyperplasia necessitates subsequent surgical excision. The most important change in our thinking about DCIS was from a monolithic view, conceiving of DCIS as a single disease highly likely to invade if left untreated, to the realization that DCIS represents a non-obligate precursor with a variable risk of progression, depending on a combination of factors, such as histology, lesion, size, and margin status. In discussing treatment options, patients should understand that local recurrence following total mastectomy is rare and that this is the procedure of choice for disease that cannot be adequately encompassed with a breast-conserving approach. If the patient and her surgeon are in agreement about proceeding with a breast-conserving approach, there needs to be a clear understanding of the incidence and implications of local recurrence. In all such discussions with newly diagnosed patients, however, it is essential to emphasize the excellent prognosis with this disease, irrespective of the surgical approach.

Biopsy, Needle↗