PubMed Health⌕ Search

Biomedical subjects

V S Klimberg

Publications and source records attributed to V S Klimberg.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Use of touch preps for intraoperative diagnosis of sentinel lymph node metastases in breast cancer.

BACKGROUND: Intraoperative touch prep (TP) is highly accurate for determining positive breast cancer margins and thereby reducing the need for second surgeries. It also may be useful in determining the status of the sentinel lymph node (SLN) during the initial surgical resection. The objective of this study was to test the ability of intraoperative TP to predict metastatic disease and, thus, the necessity for axillary lymph node dissection (ALND) at the time of SLN biopsy. METHODS: Fifty-five patients with invasive breast cancer were entered in the SLN biopsy protocol. The SLN was identified by gamma probe, dissected, and sent to pathology for TP and permanent sections. Level I and II ALND was then performed. Any radiolabeled LN in the lymphadenectomy specimen also was sent for TP and permanent sections. RESULTS: A total of 124 radiolabeled lymph nodes (LNs) were submitted for TP; of these, 93 (75%) were SLNs. Pathologic diagnosis by TP was correct compared with permanent sections for 99.2% of the nodes. There were no false positives. There was one (0.8%) false negative. The positive predictive value was 100% and the negative predictive value was 99%. Sensitivity was 95.7% and specificity was 100%. CONCLUSIONS: TP is a simple, quick, and accurate method for detecting metastatic disease in the SLN and, when used intraoperatively, enables the surgeon to determine whether or not an ALND is necessary at the time of the initial surgery.

Adult↗
PubMed1998

Sentinel lymph node biopsy for staging breast cancer.

BACKGROUND: Determination of axillary nodal status is essential for the staging of breast cancer since nodal status is one of the most important predictors of survival. The objective of this study was to test the hypothesis that the histology of the first draining lymph node (LN) accurately predicts the histology of the rest of the axillary LNs. METHODS: Fifty-five patients with operable invasive breast carcinoma and clinically negative axillary lymph nodes were studied. Patients were injected with Technetium-99 (99Tc) sulfur colloid around the primary tumor. A hand-held gamma detector probe was used to identify the sentinel LN (SLN). After the SLN was identified and removed, a level I and II lymphadenectomy was performed. RESULTS: The SLN was identified in 53 (96.3%) of the 55 patients entered into the trial. The sensitivity was 88.2% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94.6%. The accuracy of the study was 96.2%. CONCLUSIONS: The SLN biopsy for breast cancer staging is highly accurate in our hands and has the potential to decrease the morbidity and cost of managing patients with breast cancer without compromise of staging.

Adult↗
PubMed1998

Effect of glutamine on methotrexate efficacy and toxicity.

OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.

Adult↗
PubMed1996

Glutamine suppresses PGE2 synthesis and breast cancer growth.

Reduced natural killer (NK) activity found in tumor-bearing hosts has been associated with high levels of prostaglandin E2 (PGE2) produced by monocytes in vitro. We have previously demonstrated a dependence of NK cell activity on glutamine (GLN) levels in vitro and in vivo. Further, glutathione (GSH) is antagonistic to PGE2 synthesis. We hypothesized that GLN, through increased GSH production, leads to decreased PGE2 synthesis and upregulation of NK cytotoxic activity. To test this, we examined the effects of oral GLN on GSH and PGE2 concentrations, NK activity and tumor growth in a rat breast cancer model. Starting on the day of MTF-7 tumor implantation 18 Fisher 344 rats were pair-fed chow and gavaged with 1 g/kg/day GLN (n = 9) or an isonitrogenous amount of Freamine (FA) (n = 9). Seven weeks after tumor implantation rats were sacrificed. Tumors were measured, weighed, and processed for tumor morphometrics. Spleens were removed, lymphocytes isolated and assayed for NK activity. Blood GLN, GSH, and PGE2 concentrations were measured. Over the 7-week study period tumor growth was decreased by approximately 40% in the GLN-supplemented group. This decrease in growth was associated with a 2.5 fold greater NK activity in the GLN-fed rats vs FA-fed rats. This correlated with a 25% rise in GSH concentration and a proportional decrease in PGE2 synthesis. Decreased tumor volume in rats fed GLN was not associated with changes in morphometrics. Oral GLN supplementation enhances NK activity resulting in decreased tumor growth. The enhanced NK activity seen with oral GLN supplementation in the tumor-bearing host is associated with GSH mediated suppression of PGE2 synthesis.

Adenocarcinoma↗
PubMed1996

Claude H. Organ, Jr. Honorary Lectureship. Glutamine, cancer, and its therapy.

OBJECTIVE: This overview on glutamine, cancer and its therapy discusses some of the in vitro and in vivo work on glutamine and tumor growth, and summarizes animal and human data on the potential benefits of glutamine in the tumor-bearing host receiving radiation or chemotherapy. BACKGROUND: Glutamine is the most abundant amino acid in the body. A tumor can act as a "glutamine trap," depleting host glutamine stores and resulting in cachexia. In vitro evidence of the dependence of tumor growth on glutamine has deterred its use in the clinic setting. METHODS: Data from a variety of investigations studying glutamine's interaction with the tumor-bearing host receiving radiation or chemotherapy were compiled and summarized. RESULTS: A large body of evidence in vivo suggests that supplemental glutamine does not make tumors grow but in fact results in decreased growth through stimulation of the immune system. When given with radiation or chemotherapy, glutamine protects the host and actually increases the selectivity of therapy for the tumor. CONCLUSION: Further prospective randomized trials are needed to demonstrate the safety and efficacy in humans undergoing radiation and chemotherapy.

Clinical Trials as Topic↗
PubMed1995

Mycoses of the breast: diagnosis by fine-needle aspiration.

Fungal infections of the breast are unusual and may clinically mimic carcinoma. When studied by fine-needle aspiration (FNA), such masses may yield necrosis, granulomatous inflammation, reactive histiocytes, and atypical epithelial cells. Cohesive groups of atypical epithelial cells featured nuclear enlargement and overlapping, as well as prominent nucleoli. The organisms may be widely scattered, so that careful evaluation was required for their identification. In concert with provocative clinical findings, these features may lead to an erroneous diagnosis of malignancy. We describe three women with mycotic masses of the breast initially studied by FNA. The first patient presented at age 31 with a large, firm breast mass, chest wall extension, and radiographic evidence of vertebral bone involvement. FNA was requested to confirm the clinical diagnosis of advanced breast carcinoma. In addition to the atypia described above, the smears showed yeast forms indicative of blastomycosis surrounded by neutrophils. She remains well, following antifungal treatment. The second case of Blastomycosis was diagnosed by FNA of a breast mass in a 64-yr-old woman, who also responded to treatment. The third patient's preoperative needle aspiration showed granulomas, but no organisms were identified, even with special stains; silver stains of surgically excised tissue showed histoplasmosis.

Adult↗
PubMed1995

Using standardized patients to teach breast evaluation to sophomore medical students.

In response to the current emphasis on health maintenance and disease prevention, the authors developed a comprehensive education program in which sophomore medical students interview a standardized patient about breast problems and risk factors, receive one-on-one instruction from the standardized patient during the clinical breast examination, and practice recommendations for screening and instruction in breast self-examination. In this pilot study sophomore students who underwent the comprehensive education program were compared with students who received the traditional, didactic instruction and practiced on plastic breast models. The students who received the didactic instruction had mean scores on a multiple-choice knowledge-base pretest and posttest of 54.6% and 76.8%, respectively. The students who participated in the comprehensive education program had mean pretest and posttest scores of 51.2% and 78.5%, respectively. All students participated in a practical test of the clinical breast examination during an objective structured clinical examination. The students who had received the didactic instruction scored 69.9% (mean), compared with 84.1% for the students who had had the comprehensive education program. The comprehensive breast education program teaches medical students about risk factors, screening recommendations, and clinical breast examination more effectively than do traditional didactic methods.

Breast Neoplasms↗
PubMed1995

Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism.

OBJECTIVE: Chemotherapy doses are limited by toxicity to normal tissues. Intravenous glutamine protects liver cells from oxidant injury by increasing intracellular glutathione (GSH) content. The authors hypothesized that supplemental oral glutamine (GLN) would increase the therapeutic index of methotrexate (MTX) by improving host tolerance through changes in glutathione metabolism. The authors examined the effects of oral glutamine on tumor and host glutathione metabolism and response to methotrexate. METHODS: Thirty-six 300-g Fischer 344 rats were implanted with fibrosarcomas. On day 21 after implantation, rats were randomized to receive isonitrogenous isocaloric diets containing 1 g/kg/day glutamine or glycine (GLY) by gavage. On day 23 after 2 days of prefeeding, rats were randomized to one of the following four groups receiving an intraperitoneal injection of methotrexate (20 mg/kg) or saline (CON): GLN+MTX, GLY+MTX, GLN-CON, or GLY-CON. On day 24, rats were killed and studied for arterial glutamine concentration, tumor volume, kidney and gut glutaminase activity, and glutathione content (tumor, gut, heart, liver, muscle, kidney, and lung). RESULTS: Provision of the glutamine-enriched diets to rats receiving MTX decreased tumor glutathione (2.38 +/- 0.17 in GLN+MTX vs. 2.92 +/- 0.20 in GLY+MTX, p < 0.05), whereas increasing or maintaining host glutathione stores (in gut, 2.60 +/- 0.28 in GLN+MTX vs. 1.93 +/- 0.18; in GLY+MTX, p < 0.05). Depressed glutathione levels in tumor cells increases susceptibility to chemotherapy. Significantly decreased glutathione content in tumor cells in the GLN+MTX group correlated with enhanced tumor volume loss (-0.8 +/- 1.0 mL in GLN+MTX vs. +9.5 +/- 2.0 mL in GLY+MTX, p < 0.05). CONCLUSION: These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury.

Animals↗
PubMed1994

Prevention of chronic radiation enteropathy by dietary glutamine.

BACKGROUND: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. METHODS: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n = 10), GLY + XRT (n = 10), GLN only (n = 10), GLY only (n = 10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. RESULTS: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 +/- 0.48 in XRT + GLN vs. 6.42 +/- 1.55 in the XRT + GLY, p < 0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 +/- 4.3% in GLY + XRT vs. 16.0 +/- 5.1% in GLN + XRT, p < 0.05), and a 30% decrease in glutathione content (2.46 +/- 0.19 and GLY + XRT vs. 3.17 +/- 0.17 GLN + XRT, p < 0.05). CONCLUSIONS: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.

Administration, Oral↗
PubMed1992

Effect of supplemental dietary glutamine on methotrexate concentrations in tumors.

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (-GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0 +/- 0.20 nmol/g for the +GLN group vs 28.8 +/- 0.10 nmol/g for the -GLN group and 35.6 +/- 0.18 nmol/g for the +GLN group vs 32.5 +/- 0.16 nmol/g for the -GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147 +/- 0.007 microns/L for the +GLN group vs 0.120 +/- 0.006 microns/L for the -GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (-2.41 +/- 1.3 cm3 for the +GLN group vs -0.016 +/- 0.9 cm3 for the -GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 +/- 0.13 mumol/g per hour for the +GLN group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.

Animals↗
PubMed1992

Advantages of the Papillon protocol in the preoperative treatment of rectal carcinoma.

Standard treatment for advanced rectal carcinoma currently includes surgery, radiotherapy, and chemotherapy. Although there are theoretic advantages to preoperative irradiation, it is often not performed because of the prolonged delay of surgery and the purported increase in perioperative complications. A pilot study was undertaken at our institution to evaluate a treatment protocol advocated by Dr. Papillon that offers a shorter treatment time and less patient morbidity than conventional preoperative therapy for rectal carcinoma. Twenty patients with rectal cancer underwent the preoperative regimen that consisted of 3,000 cGy delivered in 10 fractions over 12 days with concomitant 5-fluorouracil and mitomycin-C. Complications were acceptable. Local recurrence was lower than in most reported trials, and survival rates were comparable. Additional benefits of the protocol include lower radiation morbidity to the patient and a decreased delay between diagnosis and surgery.

Adenocarcinoma↗
PubMed1990

Prophylactic glutamine protects the intestinal mucosa from radiation injury.

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine-enriched elemental diet, administered before whole-abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine-enriched or glutamine-free for 4 days. The animals were then subjected to a single dose of 1000 cGy x-radiation to the abdomen. After irradiation, all animals received the glutamine-free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine-fed rats. Rats receiving the glutamine-enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine-free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine-free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation effect on accelerate healing of the acutely radiated bowel.

Animals↗