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V S Klimberg

Publications and source records attributed to V S Klimberg.

At least 19 recordsLinked to original sources
PubMed2001

Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells.

BACKGROUND: Breast cancer metastasis to bone causes resorption of the mineralized matrix by osteoclasts. Macrophage colony stimulating factor (M-CSF)and receptor activator of the NF-kappaB ligand (RANKL) are produced by stromal cells and are essential for osteoclast formation. The human breast cancer cell line, MDA-MB-231, reliably forms bone metastases in a murine model and stimulates osteoclast formation in culture. We hypothesized that MDA-MB-231 stimulates osteoclast formation through secretion of M-CSF and/or RANKL. MATERIALS AND METHODS: We cocultured MDA-MB-231 and a bone marrow derived cell line, UAMS-33, and evaluated the expression of M-CSF and RANKL mRNA. Osteoclast formation was assessed using these cells added to hematopoietic cell cultures. RESULTS: MDA-MB-231 exhibited constitutive expression of M-CSF mRNA. As expected, addition of recombinant M-CSF (30 ng/ml) and RANKL (30 ng/ml) to hematopoietic osteoclast precursors supported osteoclast formation, while the addition of soluble RANKL alone or MDA-231 without added RANKL did not. Notably, coculture of MDA-231 with hematopoietic cells and added soluble RANKL stimulated significant osteoclast formation, indicating that MDA-231 served as an effective source for M-CSF. MDA-231 did not express RANKL. However, when cocultured with the murine bone marrow stromal cell line UAMS-33, RANKL expression was significantly increased in the latter cells. MDA-231 also stimulated osteoclast formation in coculture with UAMS-33 and hematopoietic cells. CONCLUSIONS: We conclude that MDA-MB-231 increases osteoclast formation by secreting adequate amounts of M-CSF protein and enhancing the expression of RANKL by stromal support cells. The ability to stimulate osteoclasts may explain the ability to metastasize to bone.

Animals↗
PubMed2001

Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism.

BACKGROUND: One mechanism of the mammary carcinogenesis of 7,12-dimethylbenz[a]anthracene (DMBA) is thought to be the generation of reactive oxygen species known to play an important role in initiation and progression. We hypothesized that DMBA would disrupt gut glutathione (GSH) metabolism and this disruption would correlate with mammary cell carcinogenesis. METHODS: Sixty-four Sprague-Dawley rats were randomized to the DMBA versus control groups. At age 50 days, rats were gavaged with a one-time dose of 20 mg DMBA or sesame oil. Rats from each group were sacrificed at 1 week (n = 16), 2 weeks (n = 16), 4 weeks (n = 16), and 11 weeks (n = 16). Tumor appearance, arterial and gut GSH concentration, and gut GSH extraction were measured over time. RESULTS: Gut GSH extraction (normally negative; production) was significantly depressed over the time points, even showing uptake (positive extraction) at Weeks 1 and 2. Tumors developed in all animals in the DMBA group by Week 11. CONCLUSIONS: A one-time oral administration of DMBA has a significant and prolonged depressive effect on gut GSH production that has not previously been described. These data support the hypothesis that the carcinogenic effect of DMBA is mediated, at least in part, by oxidative damage and that the disruption of gut GSH metabolism may play a greater role in carcinogenesis than previously realized.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Hematoma-directed ultrasound-guided breast biopsy.

OBJECTIVE AND SUMMARY BACKGROUND DATA: The standard technique for removal of nonpalpable breast lesions is needle localization breast biopsy. Because traumatic hematomas can often be seen with ultrasound, the authors hypothesized that iatrogenically induced hematomas could be used to guide the excision of nonpalpable lesions using ultrasound. METHODS: Twenty patients with nonpalpable breast lesions detected by magnetic resonance imaging only were enrolled in this single-institution trial, approved by the institutional review board. A hematoma consisting of 2 to 5 mL of the patient's own blood was injected into the breast to target the nonpalpable lesion. Intraoperative ultrasound of the hematoma was used to direct the excisional biopsy. RESULTS: The average age of women was 53.8 +/- 10 years. Ninety-five percent of lesions detected by magnetic resonance imaging were localized by hematoma injection. All the hematomas used to recognize targeted lesions were identified at surgery by ultrasound and removed without complication. Eight (40%) of the lesions were malignant, with an average tumor size of 12 +/- 6 mm (range 4-25). The remaining 12 lesions (60%) comprised papillomas, sclerosing adenosis, radial scar, fibroadenoma, and areas of atypical ductal hyperplasia. CONCLUSION: The results of this pilot study show the effectiveness of hematoma-directed ultrasound-guided breast biopsy for nonpalpable lesions seen by magnetic resonance imaging. This new procedure is potentially more comfortable for the patient because no wire or needle is left in the breast. It is technically faster and easier because ultrasound is used to visualize directly the location of the hematoma at surgery and to confirm lesion removal in the operating room by specimen ultrasound. The hematoma can be placed several days before biopsy, easing scheduling, and without fear of the migration that may occur with needle localization. This method may have ready application to mammographically detected lesions.

Adult↗
PubMed2000

Intraoperative ultrasound-guided breast biopsy.

BACKGROUND: Biopsy of nonpalpable lesions has increased during the last decade. Commonly these lesions are excised using preoperative wire localization. We describe a technique of intraoperative ultrasound-guided breast biopsy that allows easier excision and aids in obtaining surgical margins in breast cancer. METHODS: Intraoperative ultrasound was performed on 81 lesions. Ultrasound was used in an attempt to approximate a 1 cm margin on malignant lesions. RESULTS: All attempts to localize lesions with ultrasound in surgery were successful (81 of 81). Ultrasound-guided surgery was accurate in predicting margins in 24 of 25 malignant lesions. No complications resulted. CONCLUSION: Ultrasound proved to be an effective technique for localizing and excising breast lesions. Benefits may include improving patient comfort, avoiding complications of needle localization breast biopsy, and simplifying the scheduling of surgical procedures. Additionally, this procedure may be used to obtain adequate surgical margins and thus reduce the recurrence rate of breast cancer.

Adult↗
PubMed2000

Subareolar injection is a better technique for sentinel lymph node biopsy.

BACKGROUND: Numerous techniques and materials show accuracy in localizing the sentinel lymph node (SLN). We hypothesized that subareolar injection of material would localize the SLN as effectively as peritumoral injection. METHODS: Thirty-eight patients were injected with technetium-99 sulfur colloid either peritumorally or subareolarly in addition to the injection of blue dye around the tumor. Radioactive SLNs were localized using a hand-held gamma probe. RESULTS: Nineteen patients were included in each of the two groups, peritumoral and subareolar. SLNs were found in all patients injected subareolarly and in 18 of 19 injected peritumorally. The false-negative rate was 20% for peritumoral injection and 0% for subareolar injection. CONCLUSION: The results suggest that subareolar injection was as accurate, if not more accurate, than peritumoral injection for localizing the SLN. This technique is simpler than peritumoral injection and does not require injection under image guidance for nonpalpable lesions.

Adult↗
PubMed2000

Central venous catheter placement in patients with disorders of hemostasis.

BACKGROUND: Patients requiring central venous access frequently have disorders of hemostasis. The aim of this study was to identify factors predictive of bleeding complications after central venous catheterization in this group of patients. METHODS: A retrospective analysis of all central venous catheters placed over a 2-year period (1997 to 1999) at our institution were performed. The age, sex, clinical diagnosis, most recent platelet count, prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT), catheter type, the number of passes to complete the procedure, and bleeding complications were retrieved from the medical records. RESULTS: In a 2-year period, 2,010 central venous catheters were placed in 1,825 patients. Three hundred and thirty placements were in patients with disorders of hemostasis. In 88 of the 330 patients, the underlying coagulopathy was not corrected before catheter placement. In these patients, there were 3 bleeding complications requiring placement of a purse string suture at the catheter entry site. In the remaining 242 patients, there was 1 bleeding complication. Of the variables analyzed, only a low platelet count (<50 x 10(9)/L) was significantly associated with bleeding complications. CONCLUSION: Central venous access procedures can be safely performed in patients with underlying disorders of hemostasis. Even patients with low platelet counts have infrequent (3 of 88) bleeding complications, and these problems are easily managed.

Blood Coagulation Disorders↗
PubMed1999

Glutamine protects against doxorubicin-induced cardiotoxicity.

UNLABELLED: Doxorubicin (DOX) dose-intensive therapy for breast cancer is limited by a cardiomyopathy that often results in overt congestive heart failure. We hypothesized that dietary glutamine (GLN) can diminish DOX-induced cardiotoxicity by maintaining tissue glutathione (GSH) levels and thus preventing the proposed mechanism of cardiac injury: oxidation. METHODS: Forty-two female Fisher 344 rats were randomized into one of six groups: GLN + saline (SAL), GLN + DOX, freamine (FA) + SAL, FA + DOX, H2O + SAL, and H2O + DOX. Rats were pair-fed chow and gavaged with 1 g/kg/day GLN or an isonitrogenous amount of FA or H2O for 28 days. Rats were injected intravenously with a single dose of SAL or 9 mg/kg DOX on day 7 of gavage. At 28 days (21 days post-DOX), rats were sacrificed and blood and cardiac tissue were assayed for GLN and GSH content and lipid peroxidation (LP). RESULTS: There were no differences in cardiac GSH levels and cardiac lipid peroxidation in GLN + SAL versus GLN + DOX groups. However, blood and cardiac GSH levels were significantly decreased in H2O + DOX and FA + DOX groups compared to controls (H2O + SAL and FA + SAL). CONCLUSION: These data suggest that dietary GLN supplementation may diminish DOX-induced oxidative damage and thus cardiotoxicity through upregulation of cardiac GSH metabolism.

Animals↗
PubMed1999

Role of breast magnetic resonance imaging in determining breast as a source of unknown metastatic lymphadenopathy.

BACKGROUND: Occult primary breast cancer (OPBC) represents less than 1% of breast cancer. In only a third of cases, mammography identifies a primary tumor. We hypothesized that rotating delivery of excitation off-resonance breast magnetic resonance imaging (MRI) would identify or exclude the breast as a primary site in patients with OPBC. METHODS: In a retrospective review, 10 patients were identified with OPBC in which MRI was performed. Malignant appearing lesions were correlated with histopathologic findings at biopsy or surgery. RESULTS: MRI identified the primary site in 8 of 10 cases as breast (80%), and excluded it in 2 cases. The extent of disease and location was accurately predicted when compared with histopathologic specimen. CONCLUSIONS: As we continue to focus on a cure of early breast cancer, it is imperative that diagnostic images become more sensitive and specific. MRI accurately predicted OPBC in this subset of patients.

Adult↗
PubMed1999

Assessing margin status.

As little time ago as 1991 the NIH Consensus conference could not agree on the need for negative margins. Today, negative margin status has become a prerequisite for BCT recognizing that positive margins impact negatively on local recurrence rates. The science of margin evaluation is fast becoming recognized to play a key role in providing patients with the opportunity for breast conservation therapy as well as the best possible cosmetic result. Preoperative factors that predict a greater likelihood of failure to obtain margins such as larger tumor size and positive lymph nodes are fixed and can only be dealt with by taking larger biopsies. RODEO-MRI can preoperatively predict probability of success or failure and can actual better define tumor dimensions and extent and help plan excisions. Use of intraoperative US may be a future tool used to facilitate the excision of non-palpable and possibly palpable tumors. Intraoperative pathological assessment should not be performed by frozen section but consideration given to cytological assessment so as to allow feedback to the surgeon intraoperatively as to which margin needs more attention. Finally, using all the above methods of obtaining negative margins, the surgeon may have the ability to impact the outcome of breast cancer surgery and recurrence.

Biopsy, Needle↗
PubMed1999

Subareolar versus peritumoral injection for location of the sentinel lymph node.

BACKGROUND: Sentinel lymph node (SLN) biopsy is fast becoming the standard for testing lymph node involvement in many institutions. However, questions remain as to the best method of injection. The authors hypothesized that a subareolar injection of material would drain to the same lymph node as a peritumoral injection, regardless of the location of the tumor. METHODS: To test this theory, 68 patients with 69 operable invasive breast carcinomas and clinically node-negative disease were enrolled in this single-institution Institutional Review Board-approved trial. Patients were injected with 1.0 mCi of technetium-99 sulfur colloid (unfiltered) in the subareolar area of the tumor-bearing breast. Each patient received an injection of 2 to 5 cc of isosulfan blue around the tumor. Radioactive SLNs were identified using a hand-held gamma detector probe. RESULTS: The average age of patients entered into this trial was 55.2 +/- 13.4 years. The average size of the tumors was 1.48 +/- 1.0 cm. Thirty-two percent of the patients had undergone previous excisional breast biopsies. Of the 69 lesions, 62 (89.9%) had SLNs located with the blue dye and 65 (94.2%) with the technetium. In four patients, the SLN was not located with either method. All blue SLNs were also radioactive. All located SLNs were in the axilla. Of the 62 patients in which the SLNs were located with both methods, an average of 1.5 +/- 0.7 SLNs were found per patient, of which 23.2% had metastatic disease. All four patients in which no SLN was located with either method had undergone prior excisional biopsies. CONCLUSIONS: The results of this study suggest that subareolar injection of technetium is as accurate as peritumoral injection of blue dye. Central injection is easy and avoids the necessity for image-guided injection of nonpalpable breast lesions. Finally, subareolar injection of technetium avoids the problem of overlap of the radioactive zone of diffusion of the injection site with the radioactive sentinel lymph node, particularly in medial and upper outer quadrant lesions.

Adult↗
PubMed1998

The sentinel node in breast cancer--a multicenter validation study.

BACKGROUND: Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. METHODS: We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. "Hot spots" representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. RESULTS: The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status of the axillary nodes was 97 percent (392 of 405); the specificity of the method was 100 percent, the positive predictive value was 100 percent, the negative predictive value was 96 percent (291 of 304), and the sensitivity was 89 percent (101 of 114). The sentinel nodes were outside the axilla in 8 percent of cases and outside of level 1 nodes in 11 percent of cases. Three percent of positive sentinel nodes were in nonaxillary locations. CONCLUSIONS: Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient.

Axilla↗
PubMed1998

Carcinoid tumor metastatic to the breast.

Breast metastases from nonmammary malignant neoplasms are uncommon, accounting for approximately 2% of breast tumors. There are 13 cases reported in the literature of carcinoid tumor metastatic to the breast, and more than half of these cases were misdiagnosed pathologically and treated as primary breast carcinoma, even in cases with a medical record of carcinoid tumor. We describe a patient with a history of asthma and diarrhea who presented to the University of Arkansas for Medical Sciences, Little Rock, with an exacerbation of the asthma. The results of routine physical examination revealed a mass in the left breast. A diagnosis of carcinoid tumor metastatic to the breast was made after a partial mastectomy was performed. The differential diagnosis between primary carcinoid tumor of the breast and carcinoid tumor metastatic to the breast is often controversial in surgical pathology. Diagnoses need to be made correlating clinical and histological examination in difficult cases in which there is not a diagnosis of carcinoid tumor elsewhere. Accurate diagnosis of breast metastases is important to avoid unnecessary treatment.

Aged↗