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Biomedical subjects

L E Botnick

Publications and source records attributed to L E Botnick.

At least 19 recordsLinked to original sources
PubMed2000

Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node.

BACKGROUND: To the authors' knowledge it has not yet been determined which patients with primary breast carcinoma and an axillary sentinel lymph node (SN) metastasis have additional metastases in nonsentinel lymph nodes. METHODS: Pathologic features of the primary breast carcinoma and its SN metastasis were examined in 194 patients and correlated with the tumor status of the non-SNs in the same axillary basin. Two-level cytokeratin immunohistochemistry was applied to the SNs and to non-SNs of cases that were negative by standard hematoxylin and eosin examination. RESULTS: Lymph node staging based on SN findings, size of the primary tumor, and presence of peritumoral lymphatic vascular invasion (LVI) were associated with non-SN metastasis. The majority (63%) of the 101 patients with SN macrometastases had non-SN metastases. Extranodal hilar tissue invasion in conjunction with SN involvement also was strongly associated with non-SN metastasis (P = 0.0001) but was present in only 65% of patients (35 of 54 patients) with non-SN macrometastases. Approximately 26% of patients (24 of 93 patients) with SN micrometastases (</= 2.0 mm) had non-SN metastases; among these patients only primary tumor size and peritumoral LVI were correlated with non-SN metastasis. CONCLUSIONS: Detailed pathologic examination of the primary tumor and its SN metastasis may increase precision in the selection of patients for further axillary surgery or radiation therapy.

Adult↗
PubMed1986

Sequential multi-agent chemotherapy and whole abdominal irradiation for stage III ovarian carcinoma.

Modern therapy for stage III ovarian carcinoma patients usually involves one or more laparotomies with maximal resection of tumor, and intensive multi-agent chemotherapy. However, with long-term follow-up only 10-15% of patients remain free of disease. In the hope of improving outcome, we have treated 17 women with sequential multimodality therapy, including initial surgical resection (if possible), cyclophosphamide-adriamycin +/- cis-platinum, second-look surgery, and whole abdominal irradiation. Seven patients are currently alive without disease, with median follow-up of 52 months since initiation of radiation and 60 months since initiation of chemotherapy. Disease-free survival correlated with residual tumor at the start of radiotherapy: none (4/4); microscopic, less than or equal to 5 mm (3/4); greater than 5 mm or no surgery (0/9). Survival also correlated with tumor grade: grade 1 (2/2); grade 2 (2/3); grade 3 (3/11). Hematological tolerance of radiotherapy was dependent upon the number of chemotherapy cycles: ten of 11 patients receiving less than or equal to eight cycles completed radiotherapy without excessive delay, compared with only one of five receiving greater than eight cycles. There were no treatment-related deaths and only one patient required laparotomy for bowel obstruction. We conclude that intensive multimodal treatment may be tolerated moderately well if the amount of chemotherapy is limited, and that further studies are justified.

Adult↗
PubMed1986

[Reconstruction of the cervical esophagus by the free transfer of a jejunal loop. An experimental study in dogs].

A study was performed in twenty dogs in order to evaluate the chronic effects of free jejunal transfer and possible subsequent radiation therapy. Ten dogs were sacrificed within one week after surgery, three survived twelve to twenty days, and seven survived longer than six weeks with only one completing a full course of radiation equivalent to 6,000 rads to the jejunal flap. Fistulization was the most frequent complication in short-term and intermediate survivors. Inanition due to a functional rather than anatomic stenosis and dysmotility was observed in the long-term survivors. Interval oesophagoscopy and biopsy was of no additional value in evaluating flap survival. The jejunum of the animal receiving radiation showed a greater submucosal inflammatory response when compared to the other animals. Attempts at intraoperative cooling of the jejunal segment did not increase bowel survival or diminish the rate of fistulization.

Animals↗
PubMed1983

Axillary sampling in the definitive treatment of breast cancer by radiation therapy and lumpectomy.

Between January, 1967 and July, 1980, 176 women who were referred to the Joint Center for Radiation Therapy (JCRT) for definitive breast irradiation underwent low axillary dissection. A typical operative technique is described. The dissection stops short of the axillary vein although the vein is usually visualized. One hundred thirty-two axillae were thought to be N0 or N1a. Forty-six axillae were felt to be N1b. Seventeen percent of the T1 N0 patients had pathologically positive nodes. Twenty-seven percent of the T2 N0 patients had positive nodes. When 5 or less nodes were removed at axillary sampling the incidence of nodal involvement was very low. There were no differences in nodal positivity when comparing upper quadrant to lower or central lesions. Lateral lesions appeared to have higher positivity rates compared with either medial or central lesions. Ninety-four percent of axillae with N1b lesions were pathologically confirmed. The complication rate for this procedure was low. There were 5 transient non-surgical complications and 1 cellulitis resulting in a frozen shoulder, which required corrective surgery. There were no cases of moderate or severe arm edema. Axillary sampling is compared to axillary dissection as a diagnostic procedure. Axillary sampling may underestimate the true pathologic positive rate, but diagnostic accuracy appears excellent if level 1 and 2 nodes are sampled.

Axilla↗
PubMed1983

Pool size of pluripotential hematopoietic stem cells increased in continuous bone marrow culture by Friend spleen focus-forming virus.

Continuous mouse bone marrow cultures were infected with Friend murine leukemia virus. Production of nonadherent (NA) and adherent cells, granulocyte-macrophage colony-forming unit(s) of progenitor cells (GM-CFUc), pluripotential hematopoietic stem cells (CFUs), the self-renewal potential (Rs) of CFUs, and generation of factor-dependent (FD) multipotential and committed permanent stem cell cloned lines were measured. Uninfected marrow cultures from C57BL/6J, C57BL/6JUt, B6.S, C3H/HeJ, (C57BL/6J x DBA/2J)F1, CD- 1 Swiss, or N:NIH(S) mice generated NA cells, GM-CFUc, and CFUs for 20-41 weeks; cultures infected with Rauscher or other helper viruses generated them for 35-45 weeks. GM-CFUc and CFUs production in SFFV-positive cultures persisted for over 65 weeks and exceeded control levels by twentyfold to fiftyfold. The Rs of CFUs in SFFV-positive cultures was not detectably increased above control cultures. Multipotential (erythroid-neutrophil-mast cell-basophil-eosinophil) permanent FD cell clones were derived from control and SFFV-positive cultures. Thus SFFV amplifies the stem cell pool in vitro without detectably increasing the Rs capacity of CFUs.

Animals↗
PubMed1981

Differential effects of cytotoxic agents on hematopoietic progenitors.

In order to predict the effect of chemotherapeutic agents on the hematopoietic progenitor compartment, it is necessary to have a hypothesis concerning the dynamics of the cells within the compartment. By viewing this compartment as a continuum of cells with varying self-renewal capacity, one can assess the significance of the stem cell damage incurred following a single drug dose. Vinblastine, 5-fluorouracil, cyclophosphamide, busulfan, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were investigated. The acute toxicity of the drug-exposed marrow was studied by the colony-forming units-spleen (CFU-S) and agar diffusion chamber assay. Busulfan and BCNU were found to kill CFU-S preferentially. By following CFU-S recovery for 14 days post drug, different recovery patterns are noted. Busulfan and BCNU produce prolonged depression in CFU-S, whereas cyclophosphamide and 5-fluorouracil show relatively rapid recovery. If one determines the Rs (a measure of proliferative capacity) after drug, busulfan and, to a lesser extent, BCNU produce a prolonged depression without return to normal even 650 days post drug. No such depression is noted with the other drugs. The data from the recovery curves and Rs support the notion of stem cells being heterogeneous with regard to self-renewal capacity. The agar diffusion chamber and CFU-S acute survival curves would not have predicted which drugs cause significant proliferative damage. Only with the use of CFU-S recovery and ratio of CFU-S can prolonged marrow damage be ascertained.

Animals↗
PubMed1981

A regulatory mechanism for the number of pluripotential haemopoietic progenitor cells in mice.

Large changes in the pattern of regeneration of haemopoietic progenitor cells (CFU-S) are reported as a result of simply altering the time interval between administration of certain cytotoxic agents and whole-body irradiation. These results suggest a negative feedback control for the number of CFU-S, which has an appreciable time delay. A high inverse correlation between the number of maturing granulocytic cells (with ring-shaped nuclei) at the time of irradiation and the subsequent regeneration of CFU-S is consistent with these cells producing some substance that controls the number but not the proliferation rate of the CFU-S. The possibility is considered that this mechanism is an important control in the biological regulation of haemopoiesis.

Animals↗
PubMed1979

Nature of the hemopoietic stem cell compartment and its proliferative potential.

The nature of the hemopoietic stem cell compartment has been the subject of much controversy. Data are presented to support the concept of a 'continuum' model of the stem cell compartment. The important characteristics of this model are that within the continuum there are cells with varying proliferative capacities. As cells move through the compartment, their proliferative capacity becomes more limited, their likelihood to be in cycle increases, and their commitment to a specific differentiated pathway increases. Experiments with busulfan, cyclophosphamide, 5-flurouracil, and BCNU demonstrate defects in proliferative potential of the surviving CFU-S population. These defects persist throughout the life of the animal without any evidence of recovery. The clinical implications of late stem cell failure may be important as a consideration in the use of cytotoxic agents.

Animals↗
PubMed1979

Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow.

Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

Animals↗
PubMed1978

Proliferative capacity of murine hematopoietic stem cells.

The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferative quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cell progress in the continuum in one direction and such progression is not reversible.

Animals↗
PubMed1977

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive, without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.

Adolescent↗