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Biomedical subjects

D N Krag

Publications and source records attributed to D N Krag.

At least 55 records · Page 3Linked to original sources
PubMed1993

Gamma-probe-guided lymph node localization in malignant melanoma.

The initial draining lymph node (sentinel node) has been successfully localized using intraoperative vital dye mapping and reportedly is predictive of regional nodal metastases in Clinical- Stage 1 melanoma. In an animal model, we previously established the technique of gamma-probe-guided localization of the technetium-99 sulfur colloid labelled sentinel node and found its sensitivity equal to vital dye mapping. We now report our initial experience using gamma-probe-guided localization to identify and then surgically remove the first draining lymph node(s) in 10 malignant melanoma patients. Lymphoscintigraphy was used to confirm localization. We conclude that this technique: (a) reliably localizes the sentinel node draining the site of a primary melanoma, (b) allows the lymphatic bed to be checked intraoperatively verifying complete sentinel node biopsy, and (c) is relatively simple and can be performed under local anaesthesia.

Adult↗
PubMed1993

Clinical utility of immunoscintigraphy in managing ovarian cancer.

Ovarian cancer spreads to multiple areas of the peritoneal cavity early in the course of the disease. Multiple small foci of tumor are not identified readily with standard preoperative staging procedures. A review of an immunoscintigraphy study of more than 100 women preoperatively staged with 111In-labeled B72.3 (CYT-103) reveals that this technique has a low potential for serious side effects and it can identify miliary spread of ovarian cancer and extra-abdominal metastases. It has the potential to contribute favorably to patient management by detecting occult lesions, may define the extent of tumor as well or better than computerized tomography and may impact on surgical decision-making.

Aged↗
PubMed1992

Gamma probe location of 111indium-labeled B72.3: an extension of immunoscintigraphy.

Eight colorectal and 5 ovarian cancer patients were evaluated with preoperative immunoscintigraphy and intraoperative gamma probe detection of 111indium-labeled monoclonal antibody B72.3. Immunoscintigraphy detected the presence of tumor in every patient shown to have tumor at surgery. There was one false-positive scan. A total of 21 pathologically verified lesions were identified at surgery in the 11 patients with tumor. Immunoscintigraphy localized 12 (57%) and intraoperative gamma probe detection located 17 (81%) of the lesions. Intraoperative probe detection located 6 of 8 lesions smaller than 1 cm and 3 lesions that were not identified on initial surgical exploration. The gamma probe offers information that is complementary to immunoscintigraphy in that (1) it aids the surgeon in locating intra- and extra-abdominal lesions previously identified by immunoscintigraphy, (2) it locates lesions too small to be seen by immunoscintigraphy alone, (3) it locates lesions that otherwise might be missed at surgery, and (4) it provides objective evidence for adequacy of surgical resection of cancer in the abdominal cavity.

Aged↗
PubMed1992

A simplified technique to resect abnormal bony radiolocalizations using a gamma counter.

A simplified technique for localizing and verifying the correct biopsy site of lesions identified on a bone scan has been utilized. A hand-held gamma counter was used for localization of incision placement, determination of extent of bone to be resected, and verification that appropriate tissue was resected. This technique was used to guide biopsy of bony lesions in five patients and to guide resection of a pubic ramus chondrosarcoma. We conclude that intraoperative use of a gamma counter to guide biopsy of bony lesions minimizes surgery time, increases the confidence of obtaining correct tissue, and makes a frequently frustrating procedure very simple. In addition, the probe may assist with determining adequate margins at definitive resection of tumours which accumulate technetium-99m MDP.

Adult↗
PubMed1992

Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT.

Immunoscintigraphy performed after intravenous administration of indium-111-labeled CYT-103, an immunoconjugate of monoclonal antibody B72.3, was evaluated in patients with suspected primary or recurrent colorectal cancer at 25 centers in the United States. Gamma camera imaging, computed tomography (CT), and confirmatory surgical exploration were completed in 169 of 227 patients who received single infusions of In-111 CYT-103. Eight patients (3.5%) had reversible, nonserious adverse reactions, and 39% developed antimurine antibodies. Surgery revealed that 155 of 169 patients had colorectal carcinoma. In these 155 patients, immunoscintigraphy and CT demonstrated similar sensitivity (69% and 68%, respectively) and specificity (77%). However, immunoscintigraphy had greater sensitivity in detection of pelvic tumors (74% vs 57%, P = .035) and extrahepatic abdominal tumors (66% vs 34%, P less than .001); CT enabled detection of a greater proportion of liver metastases (84% vs 41%, P less than .001). These results indicate that In-111 CYT-103 can be administered safely and that immunoscintigraphy performed with this agent frequently enables identification of extrahepatic abdominal sites of disease not visualized with CT.

Adult↗
PubMed1991

Composite tissue transfer in limb-salvage surgery.

After extensive resection due to extremity sarcoma, the inability to cover the defect for satisfactory healing and limb function has been an indication for amputation rather than limb salvage. We report herein our experience with seven limb-salvage cases in which we closed difficult and complex defects with composite tissue transfers utilizing microvascular techniques. Free-flap transfers were used to cover soft-tissue defects after extensive resection of primary and locally recurrent tumor and to manage radiation-induced complications. The grafts healed well when infected irradiated tissue was covered, and the grafts tolerated postoperative irradiation. Composite tissue transfer also provided soft-tissue coverage around distal joints that would not have been adequately protected with a skin graft. Complications were minimal, and all patients maintained good extremity function. No patient who underwent composite tissue transfer has had a local recurrence. A free-flap composite tissue transfer can extend the indications for limb-salvage surgery and offers an alternative to amputation in selected patients.

Adolescent↗
PubMed1991

Heterogeneity of heat response in murine, canine and human tumors: influence on predictive assays.

The heterogeneity of response to hyperthermia of cells taken from different regions of tumors was tested in a model tumor system (RIF-1) in the mouse and in specimens from spontaneous tumors taken from dogs and humans at the time of surgical resection. Cell survival was assayed by clonogenic survival in the murine tumor and by dansyl lysine staining in tumors from all three species. Using survival as an endpoint, it was found that the extent of heterogeneity depended on the temperature to which the tumor was heated and the duration of exposure. By increasing either of these factors, the coefficient of variation was increased. The large heterogeneity seen after in vivo heating could not be explained entirely by inhomogeneous heating within the tumor as evidenced by temperature mapping. It is concluded that other microenvironmental factors such as blood flow, pH, O2, and nutrient supply may cause variations in the heat response of the tumor cells in vivo. Little, if any, evidence of cellular heterogeneity was evident for all three species when comparisons were made between samples of 100-200 mg. The canine and human tumors were considerably more heat resistant when dansyl lysine was used as an endpoint. In the RIF-1 tumors, heterogeneity of heat response was greater after in vitro heating than after in vivo heating when small biopsy samples (10-20 mg) were taken, suggesting that some cellular heterogeneity was present.

Animals↗
PubMed1990

Hyperthermic enhancement of rhodamine 123 cytotoxicity in B16 mouse melanoma cells in vitro.

The effect of elevated temperature on cytotoxicity of rhodamine 123 (R123) was tested in vitro on B16 mouse melanoma cells. Simultaneous 1-h exposure to R123 and hyperthermia (43 degrees C for 1 h) resulted in marked enhancement of R123 cytotoxicity. Thermal enhancement of R123 cytotoxicity occurred at temperatures as low as 38 degrees C. Heat treatment (43 degrees C for 1 h) given immediately before or after R123 exposure (37 degrees C for 1 h) yielded no significant increase in cytotoxicity over that expected for strict additivity. The effects of heat on two mechanisms reported to be associated with R123 cytotoxicity were evaluated: (a) target inactivation by R123; and (b) R123 intracellular accumulation. Hyperthermia caused an increased rate of target inactivation by R123 and also caused an increased net intracellular accumulation of R123. This indicates that at least two mechanisms are responsible for the synergistic cytotoxicity of R123 and hyperthermia.

Animals↗
PubMed1990

In vitro and in vivo cytotoxicity of rhodamine 123 combined with hyperthermia.

Because both Rhodamine 123 (R123) and hyperthermia have been shown to be cytotoxic, we examined their effect, independently and in combination, on five different human malignant cell lines in vitro and on cultured melanoma cells grown intradermally in nude mice. The cell lines examined include two human melanomas, UCLA-SO-M14 and UCLA-SO-M21, the colon cancer cell line HT29, the human lung cancer cell line P3, and the human breast cancer cell line B231. R123 and hyperthermia, when used in combination, were found to be cytotoxic for these five different human malignant cell lines in vitro. The two agents together appear to enhance the cytotoxic effect of each alone, as documented by synergistic ratios ranging from 2.31 to 45 for the different cell lines. In the "nude" mouse model, animals were treated with a combination of R123 and hyperthermia (43 degrees C for 90 min). A statistically significant (P = 0.04) decrease in tumor growth rate was observed when compared with the rate of tumor growth in untreated animals. The results suggest a potential role for R123 in combination with hyperthermia in the treatment of malignant cells.

Animals↗
PubMed1990

Intralesional cis-diamminedichloroplatinum and purified collagen treatment of human metastatic malignancies: a feasibility study.

A feasibility study of the treatment of advanced superficial human malignant tumors utilizing direct intralesional injections of cisplatin mixed with purified bovine collagen was performed. The purpose of using intralesional injection of cisplatin mixed with collagen was to limit the drug exposure to normal tissues while increasing the dose and duration of exposure to the tumor. Fourteen evaluable superficial tumors in four patients (melanoma, breast CA, squamous CA from larynx) received a total of 65 treatments in the outpatient clinic setting. All patients had failed prior treatment with systemic intravenous cisplatin. Lesions were treated at least three times at two-week intervals. After intramuscular meperidine premedication, multiple injections of cisplatin mixed with collagen were made into the tumors. There was minimal normal tissue toxicity and minimal systemic toxicity. Tumor regression or stabilization occurred in 86% (12/14) of tumors; 50% (7/14) of lesions regressed more than 50% in size. This study suggests that intralesional colloidal cisplatin can overcome resistance to systemic intravenous cisplatin.

Adenocarcinoma↗
PubMed1989

Relationship between cellular accumulation of rhodamine 123 (R123) and cytotoxicity in B16 melanoma cells.

Rhodamine 123 (R123) is a mitochondria-specific prototype anticancer agent because its target is the energy-producing mechanism of the cell. The goal of this study was to investigate the relationship between intracellular R123 accumulation and cytotoxicity in a R123-sensitive cell line (RS) and a R123-resistant subline (RR) that we developed. Cytotoxicity after exposure to R123 (0-60 micrograms/ml) was assessed using the clonogenic assay. Intracellular R123 was extracted with acid-alcohol and measured by fluorimetry. The rate of R123 accumulation over 1 hr was significantly higher (P less than 0.0001) for RS cells (4.65 +/- 0.39 micrograms/min/10(6) cells) than for RR cells (1.29 +/- 0.24 micrograms/min/10(6) cells). R123 accumulation in RS cells was strongly correlated (r = 0.80; P less than 0.0001) with cytotoxicity. Treatment of RR cells with verapamil (100 microM) reversed R123 resistance. The resulting dose-survival curve was identical to the dose-response curve of RS cells treated with R123 alone. Cellular content of R123 in RR cells treated with verapamil increased to a level similar to that of RS cells and correlated with cytotoxicity. These data suggest that cytotoxicity of R123 in B16 cells results from increased cellular accumulation of R123.

Animals↗
PubMed1988

Thermal resistance of human malignant melanoma modulated by prostaglandin E2.

The inhibition of DNA synthesis in a human malignant melanoma cell line as measured by tritiated thymidine (3H-TdR) incorporation was both time- and temperature dependent. Two components of cell damage were identified: a cytostatic, temporary component from which cells recovered within 2-6 days, and a cytotoxic, permanent component from which no recovery was observed. Thermotolerance was induced in M14 cells by sublethal heat treatment at 41 degrees C for 1 hr. However, induction of thermotolerance was blocked by indomethacin, a prostaglandin synthetase inhibitor. Exogenous PGE2 at concentrations up to 10 micrograms/ml also protected cells from heat damage. These data suggest that prostaglandin synthesis increases during heat stress and may play a role in protecting cells from thermal damage.

Dinoprostone↗
PubMed1986

Effect of localized magnetic-induction hyperthermia on the brain. Temperature versus intracranial pressure.

Normal brain and brain tumor temperatures were studied for their effects on intracranial pressure (ICP) in 13 patients who received 37 localized thermochemotherapy treatments for recurrent primary or metastatic brain tumors. Two transient neurologic complications occurred in patients with an elevated initial ICP value; thus, the authors concluded that an initial ICP value of 30 cm H2O or greater may contraindicate brain hyperthermia. It appears that noninvasive brain hyperthermia by magnetic-loop induction can cause an initial rise in ICP value, although a protective mechanism(s) that tends to lower ICP occurs over time, and also at a normal brain temperature of approximately 42.0 degrees C. Possible mechanisms of ICP reduction include direct heating of the hypothalamus with a reduction in pCO2 and the development of tachypnea and hyperpnea with a reduction in pCO2. Hyperthermia applied to the brain should be undertaken only with adequate monitoring of ICP; in addition, extreme caution should be taken in patients with an elevated initial ICP value and in those patients in whom adaptation to elevated pressure does not occur.

Adult↗
PubMedDate not supplied

Sentinel lymph node--why study it: implications of the B-32 study.

Surgical removal of the regional lymph nodes by a level I and level II axillary dissection remains the standard of care for patients with surgically resectable breast cancer. Axillary dissection provides accurate pathologic staging and excellent regional disease control, and likely provides a small benefit in patient survival. Axillary dissection, however, is associated with significant patient morbidity. Sentinel lymph node (SLN) biopsy procedures have been found to provide very accurate pathologic staging when compared to axillary dissection; however, their effect on regional disease control and patient survival is not yet known. The National Cancer Institute (NCI) has sponsored a Phase III prospective, randomized clinical trial (the B-32 trial) through the National Adjuvant Breast and Bowel Project (NSABP), to compare results of patients treated with SLN biopsy alone vs. SLN biopsy with completion axillary node dissection in patients with clinically node-negative breast cancer. Results of this trial will provide evidence of the safety of SLN biopsy procedures in the management of patients with breast cancer.

Breast Neoplasms↗
PubMedDate not supplied

Guidelines for the safe use of radioactive materials during localization and resection of the sentinel lymph node.

BACKGROUND: Several reports have demonstrated accurate prediction of nodal metastasis with radiolocalization and selective resection of the radiolocalized sentinel lymph node (SLN) in patients with breast cancer and melanoma. As reliance on this technique grows, its use by those without experience in radiation safety will increase. METHODS: Tissue obtained during radioguided SLN biopsies was examined for residual radioactivity. Specimens with a specific activity greater than the radiologic control level (RCL) of 0.002 microCi/g were considered radioactive. Radiation exposure to the surgical team was measured. RESULTS: A total of 24 primary tissue specimens and 318 lymph nodes were obtained during 57 operations (37 for breast cancer, 20 for melanoma). All 24 (100%) of the specimens injected with radiopharmaceutical and 89 of 98 (91%) of the localized nodes were radioactive after surgery. Activity fell below the RCL 71+/-3.6 hours in primary tissue specimens, 46+/-1.7 hours in nodes from melanoma patients, and 33+/-3.5 hours in nodes from breast cancer patients (P = .037). The hands of the surgical team (n = 22 cases) were exposed to 9.4+/-3.6 mrem/case. CONCLUSION: Although low levels of radiation exposure are associated with radiolocalization and resection of the SLN, the presented guidelines ensure conformity to existing regulations and allow timely pathologic analysis.

Biopsy↗
PubMedDate not supplied

Induction of transient hyperglycaemia in cancer patients.

Serum glucose levels up to 700 mg/dl were achieved and maintained for 3 h in patients with advanced metastatic cancer by infusion of concentrated glucose solutions. Even with infusions of large amounts of glucose, the maximum sustainable level of serum glucose did not exceed 700 mg/dl. The apparent ceiling of serum glucose level appeared to be due to a large and rapid loss of glucose from the kidneys. With adequate fluid volume replacement there was no rebound hypoglycaemia and there was no significant changes in haematocrit or electrolytes.

Blood Glucose↗
PubMedDate not supplied

Reversal of thermochemotherapeutic resistance to rhodamine 123 by verapamil.

Rhodamine 123 (R123) cytotoxicity and intracellular accumulation were studied at elevated temperature in R123-sensitive and R123-resistant B16 mouse melanoma cell lines. Hyperthermic potentiation of R123 cytotoxicity, present in the parental R123-sensitive cell line, was not present in the R123-resistant cell line. R123-resistant melanoma cells did not develop concomitant resistance to hyperthermia. Hyperthermic potentiation of R123 cytotoxicity was restored in the resistant cells by co-treatment with verapamil. Restoration of hyperthermic potentiation of R123 by verapamil in R123-resistant cells was accompanied by increased intracellular accumulation and decreased efflux of R123. These results suggest that verapamil may be used to re-establish thermal enhancement of drug cytotoxicity when thermochemotherapeutic resistance is present.

Animals↗