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D N Krag

Publications and source records attributed to D N Krag.

At least 19 recordsLinked to original sources
PubMed2001

Radiolabeled sentinel node biopsy: collaborative trial with the National Cancer Institute.

The objective of this study was to maximize the success rate of sentinel node (SN) localization in breast cancer patients with the tracer that demonstrated the highest initial success during a preliminary evaluation. Altogether, 145 patients with operable invasive breast cancer and clinically negative lymph nodes were studied. Technetium 99m (99mTc)-sulfur colloid was injected into the breast parenchyma surrounding the invasive cancer or the biopsy cavity. Variable volumes of tracer, amounts of 99mTc, and duration of time between injection and surgery were evaluated. A hand-held gamma detector was used at surgery to locate and guide resection of all radioactive sentinel nodes (SNs), including those that were extraaxillary. A conventional lymphadenectomy was then performed in all cases. Based on previous studies, unfiltered sulfur colloid provided a higher success rate of SN identification than the other tracer types. Further evaluation with 99mTc-sulfur colloid demonstrated that increased volume increased the success rate of SN identification. An injection volume of 8 ml resulted in a success rate of 98%. SNs were not exclusively located in the axilla: In 8.6% of cases SNs were removed from an internal mammary location. The overall accuracy of patients with SNs resected was 98.4%, and the false-negative rate was 4.4%. It was concluded that (1) unfiltered 99mTc-sulfur colloid at a volume of 8 ml resulted in a high success rate for SN identification; (2) a significant number of the SNs were extraaxillary in location; and (3) the accuracy of the SNs for determining whether regional metastases had occurred was high. The U.S. National Cancer Institute is funding a randomized phase III clinical trial to evaluate SN resection compared to conventional axillary lymphadenectomy in clinical node-negative breast cancer patients. Major endpoints of this trial include long-term regional control and survival.

Breast Neoplasms↗
PubMed2001

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Chi-Square Distribution↗
PubMed2001

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Adolescent↗
PubMed2001

Tamoxifen and cardiac risk factors in healthy women: Suggestion of an anti-inflammatory effect.

-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.

Administration, Oral↗
PubMed2001

Sentinel lymph node biopsy in breast cancer.

Sentinel lymph node biopsy techniques have evolved in a short period of time to become a highly accurate method for the pathologic staging of clinically node-negative breast cancers. Multiple single and multi-institutional studies have confirmed a high accuracy of pathologic staging (95-100%) with reasonable false-negative rates (0-15%). The use of vital blue dyes, radioactive isotopes, or a combination of the two are the most commonly employed techniques used for this procedure. Currently, two large prospective randomized Phase III clinical trials supported by the National Cancer Institute are underway, which will define the effectiveness of these techniques as compared to standard axillary dissection in regards to regional disease control and patient survival.

Journal Article↗
PubMed2000

Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study.

BACKGROUND: Axillary lymph node status is a powerful prognostic factor in breast carcinoma; however, complications after axillary lymph node dissection are common. Sentinel lymph node biopsy is an alternative staging procedure. The sentinel lymph node postulate is that tumor cells migrating from the primary tumor colonize one or a few lymph nodes before colonizing subsequent lymph nodes. To validate this hypothesis, the distribution of occult and nonoccult metastases in sentinel and nonsentinel lymph nodes was evaluated. METHODS: Original pathology material was reviewed from 431 patients enrolled on a multicenter validation study of sentinel lymph node biopsy in breast carcinoma patients. Paraffin embedded tissue blocks of sentinel and nonsentinel lymph nodes were obtained for 214 lymph node negative patients. Additional sections from 100 and 200 microm deeper into the paraffin block were examined for the presence of occult metastatic carcinoma. Both routine and cytokeratin immunohistochemical stains were employed. RESULTS: Metastases were identified in 15.9% of sentinel lymph nodes and 4.2% of nonsentinel lymph nodes (odds ratio [OR] 4.3[ P < 0.001]; 95% confidence interval [95% CI], 3.5-5.4). Occult metastases were identified in 4. 09% of sentinel lymph nodes and 0.35% of nonsentinel lymph nodes (OR 12.3 [P < 0.001]; 95% CI, 5.6-28.6). The overall case conversion rate was 10.3%. All the occult metastases identified were < or = 1 mm in greatest individual dimension. The likelihood (OR) of metastases in nonsentinel lymph nodes was 13.4 times higher for sentinel lymph node positive than for sentinel lymph node negative patients (P < 0. 001; 95% CI, 6.7-28.1). CONCLUSIONS: The distribution of occult and nonoccult metastases in axillary lymph nodes validates the sentinel lymph node hypothesis. In addition, pathology review of cases confirmed the authors' previously reported finding that the sentinel lymph nodes are predictive of the final axillary lymph node status. Occult metastatic disease is more likely to be identified in sentinel lymph nodes, allowing future studies to focus attention on one or a few sentinel lymph nodes. However, the relation between occult metastatic disease in sentinel lymph nodes, disease free survival, and overall survival must be evaluated prior to endorsing the intensive analysis of sentinel lymph nodes in routine practice. [See editorial on pages 971-7, this issue.]

Axilla↗
PubMed2000

Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.

OBJECTIVES: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease. STUDY DESIGN: A prospective report on the application sentinel node radiolocalization in eight patients with N0 squamous cell carcinoma of the head and neck region. METHODS: For each patient a peritumoral submucosal injection of filtered technetium (99mTc) prepared with sulfur colloid was performed immediately following intubation. After at least 30 minutes, focal areas of accumulation corresponding to a sentinel node were marked on the skin surface. Complete neck dissections were performed, and the sentinel nodes were identified for later histological evaluation and comparison to the remaining lymphadenectomy specimen. RESULTS: Sentinel node radiolocalization accurately identified two or more sentinel lymph nodes in all eight cases. In one patient, two of the three lymph nodes containing micrometastatic disease were sentinel lymph nodes. There was no instance in which sentinel node was negative for micrometastatic disease while being positive in a nonsentinel lymph node. CONCLUSIONS: Accurate localization of the sentinel lymph node using radiolabeled sulfur-colloid is feasible in patients with squamous cell carcinoma of the head and neck region. Although sentinel node radiolocalization in head and neck squamous cell cancer may potentially reduce the time, cost, and morbidity of regional lymph node management, more experience with technique is required before its role can be determined.

Aged↗
PubMed1999

Unfiltered sulfur colloid and sentinel node biopsy for breast cancer: technical and kinetic considerations.

BACKGROUND: There are few clinical data on technical limitations and radiocolloid kinetics related to sentinel lymph node (SLN) biopsy for breast cancer. METHODS: In 70 clinical node-negative patients, unfiltered 99mTc sulfur-colloid was injected peritumorally and cutaneous hot spots were mapped with a gamma probe. SLN biopsy was performed followed by axillary lymph node dissection. Missed radioactive nodes (nodes not under hot spots) were removed from axillary lymph node dissection specimens and submitted separately. RESULTS: At least one hot spot was mapped in 69 patients (98%) and SLNs were retrieved in 62 (89%). No radiolabeled nodes were found in five (7%) and only nodes not under hot spots were retrieved in three patients (4%). Residual nodes not under hot spots were retrieved in 17 patients (24%) in whom at least one SLN specimen had been found. Diffuse radioactivity around the radiocolloid injection site impeded identification of all radiolabeled nodes during SLN biopsy, and was responsible for one of two false negatives (20 node-positive patients; false-negative rate 10%). Hot spot radioactivity, number of radiolabeled nodes, and nodal radioactivity did not change with time interval from radiocolloid injection to surgery (0.75-6.25 hours). CONCLUSIONS: Although SLN localization rate is high, intraparenchymal injection may predispose to failure of radiocolloid migration, failure to identify SLNs because of high radiation background, and false-negative outcomes. Alternative routes of radiocolloid administration should be explored.

Adult↗
PubMed1999

Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy.

BACKGROUND: Radiolocalization and selective biopsy of the sentinel node to correctly predict the status of remaining lymph nodes may provide an alternative to axillary dissection in selected breast cancer patients with clinically negative lymph nodes. STUDY DESIGN: In a nonrandomized, multicenter clinical trial, gamma probe localization for lymphatic mapping and sentinel node biopsy along with axillary dissection was performed on 75 patients with invasive breast cancer and clinically negative lymph nodes. The accuracy of the sentinel node biopsy to correctly predict the status of the remaining axillary lymph nodes was established through standard pathologic investigation. RESULTS: A sentinel node was identified in 70 of 75 patients with a technical success rate of 93%. Of these 70 patients, 21 (30%) had axillary nodal metastases identified pathologically. Four of these 21 (19%) had sentinel nodes negative for metastases. All 4 false-negative patients had prior excisional biopsies. The false-negative group had a larger mean maximal biopsy dimension than the true-positive group. Eleven of the 21 patients with axillary metastases had a diagnosis made by core needle biopsy with no false negatives. CONCLUSIONS: The accuracy of the sentinel node biopsy in correctly predicting the status of remaining axillary lymph nodes may be limited in patients with large excision before radiolocalization of the sentinel node. Our findings suggest that excisional biopsy should be avoided prior to lymphatic mapping for sentinel node biopsy.

Adult↗
PubMed1999

Intraoperative ultrasound localization to guide surgical excision of nonpalpable breast carcinoma.

BACKGROUND: This report describes a technique of intraoperative tumor localization by ultrasound without the use of a needle or wire to guide the excision of nonpalpable breast cancers. The results of our experience with pathologic margin status are reviewed. STUDY DESIGN: From 1994 to 1998, 65 breast cancers in 62 patients with biopsy-proved nonpalpable breast cancer were excised using intraoperative ultrasound localization. The pathologic status of the margins from the initial surgical excision specimen and any further excisions, either at the first operation or later procedures, was recorded. The distance from the tumor to the closest margin of excision was also determined. RESULTS: The overall success in achieving pathologically negative excision margins at first operation was 97% (63 of 65 cancers). Three patients underwent a second operative procedure, two for positive margins and one for a margin less than 1 mm (second operation = 4.8% of patients). After completion of the first operative procedure, the mean distance to the closest margin of excision was 0.8 cm. CONCLUSIONS: Intraoperative ultrasound localization for excision of nonpalpable breast cancers is feasible and gives results, in terms of pathologic margins, that are comparable with those achieved by standard needle-wire-guided excisions.

Adult↗
PubMed1999

Adjustment to breast cancer: age-related differences in coping and emotional distress.

Women who are diagnosed with breast cancer are at high risk for experiencing affective distress; however, previous research suggests that older women may be less likely than younger women to experience extreme distress. Two issues remain unclear regarding age and affective distress: (a) the psychological processes that account for the association of age and distress, and (b) whether this association remains stable over the course of treatment and recovery from breast cancer. This study investigated symptoms of anxiety and depression in 80 women ages 36-80 years old with newly diagnosed breast cancer near the time of their diagnosis and at 3 and 6 months post-diagnosis. Disease severity and coping style were also examined. Symptoms of anxiety/depression and age were negatively correlated near the time of diagnosis. Path analysis controlling for disease severity revealed that coping involving the ventilation of emotion fully mediated the effect of age on symptoms of anxiety and depression. However, the association of age with symptoms of anxiety/depression was no longer significant at 3 and 6 months post-diagnosis, although emotional ventilation still predicted greater emotional distress at 6 months. These findings suggest that age is a salient factor to consider in the psychological adjustment of women with breast cancer near the time of initial diagnosis, with younger women exhibiting greater affective distress and a tendency to engage in less adaptive ways of coping. However, younger and older women do not differ in their adjustment over the subsequent course of their treatment and initial recovery. The use of emotional ventilation coping remains associated with poorer adjustment, independent of patients' age.

Adaptation, Psychological↗
PubMed1999

Psychological adjustment in breast cancer: processes of emotional distress.

The process of psychological adjustment to breast cancer was examined at diagnosis and at 3- and 6-month follow-ups in a sample of 80 women with Stage I-Stage IV breast cancer. At diagnosis, symptoms of anxiety/depression were predicted by low dispositional optimism, and this path was partially mediated by use of emotion-focused disengagement coping. Younger age also was predictive of anxiety/depression symptoms at time of diagnosis, and this relationship was fully mediated by magnitude of intrusive thoughts. At 3 months, changes in anxiety/depression symptoms were predicted only by intrusive thoughts. At 6 months, low dispositional optimism reemerged as a significant predictor of changes in anxiety/depression and again was partially mediated by the use of emotion-focused disengagement coping. Independent effects for problem-focused engagement and disengagement and emotion-focused engagement coping were also found at 6 months. Implications of these data for psychosocial interventions with breast cancer patients are highlighted.

Adaptation, Psychological↗
PubMed1999

Gamma probe localization of cranial bone lesions.

PURPOSE: Staging of cancer is essential to formulate appropriate treatment plans and to help predict prognosis. A solitary region of increased radionuclide uptake ("hot spot") on a bone scan may represent a metastasis or a masquerading lesion. Biopsy may be required to determine its histologic nature, but localization of the site may be difficult because bone scans provide poor spatial resolution. METHODS: In two patients with breast carcinoma, radioactive technetium was administered intravenously and a gamma probe was used preoperatively and intraoperatively to identify the site of cranial bone involvement. RESULTS: The lesions were resected; one was a benign fibro-osseous lesion and one was a metastatic breast adenocarcinoma. CONCLUSIONS: A gamma probe may be helpful in localizing the site of radioactive uptake identified by bone scan.

Adenocarcinoma↗
PubMed1999

Sentinel lymph node biopsy for breast cancer: the role of previous biopsy on patient eligibility.

Several reports have demonstrated the accurate prediction of axillary nodal status with radiolocalization and selective resection of sentinel lymph nodes (SLNs) in patients with breast cancer (BC). Because of concerns over lymphatic disruption, several authors have proposed that prior excisional breast biopsy is a contraindication for SLN biopsy. Clear unfiltered 99mtechnetium-sulfur colloid (1.0 mCi) was injected around the perimeter of the breast lesion (palpable and nonpalpable) or prior biopsy site. Resection of the radiolocalized SLN was then performed. Axillary lymph node dissection was performed immediately after SLN biopsy in the first 57 patients. Eighty-two BC patients underwent SLN biopsy. The SLN was localized in 98 per cent (80 of 82). The type of previously performed diagnostic biopsy or the location of the primary lesion did not influence the ability to localize the sentinel lymph node. In the 57 patients who had axillary lymph node dissection, metastatic disease was identified in 23 per cent (13 of 57). Axillary nodal status was accurately predicted in 98 per cent (56 of 57). Early experience with radiolocalization and selective resection of SLN in BC remains promising. By demonstrating the effective localization of the SLN regardless of the extent of prior biopsy, these data support expanding the number of patients potentially eligible for SLN biopsy.

Axilla↗
PubMed1999

Submission of lymph node tissue for ancillary studies decreases the accuracy of conventional breast cancer axillary node staging.

Pathologists are under increasing pressure to submit fresh tissue for ancillary studies and research protocols. In several tumor types (breast, lung, melanoma, colorectal, prostate), increased interest in detecting submicroscopic nodal metastases through reverse transcriptase polymerase chain reaction analysis of mRNA from portions of lymph nodes has precluded histologic analysis of the entire node for metastases. A retrospective review was undertaken of 227 breast cancer patients prospectively entered on a research protocol examining the usefulness of sentinel lymph node surgery. All of the patients ultimately underwent complete lymph node dissection. The research protocol required that all nodes greater than 8 mm in size be bisected and submitted separately. Positive lymph nodes were evaluated for unilateral or bilateral involvement in the node sections. Sixty node-positive patients were identified, yielding 230 positive nodes. One hundred seven of these nodes were confirmed to have been bisected. Carcinoma was identified in both lymph node sections in 64 (59.8%) nodes and in only one-half of the bisected lymph node in 43 (40.2%) nodes. Involvement of both sections was more likely when patients had multiple nodes positive. In 12 patients, involvement of one-half of the bisected nodes was the only evidence of metastatic disease (20.0% of node-positive patients). This evidence suggests that submission of less than the complete lymph node for histologic evaluation of metastatic disease decreases the accuracy of lymph node staging. Furthermore, a significant proportion of patients may be erroneously classified as histologically node negative.

Adult↗
PubMed1998

Localization of regional lymph nodes in melanomas of the head and neck.

OBJECTIVES: To study the efficacy of gamma-probe radiolocalization of the first draining (sentinel) lymph node (SLN) in stage N0 melanoma of the head and neck and to evaluate its potential role in the staging and treatment of this disease. DESIGN: Gamma-probe radiolocalization, a new alternative to blue-dye lymphatic mapping, uses a scintillation (gamma) probe to identify radiolabeled SLNs. In a consecutive sample clinical trial, gamma-probe radiolocalization of the SLN is compared with lymphoscintigraphy and blue-dye lymphatic mapping. Follow-ups ranged from 1.7 years to 4 years, with a mean follow-up of 2.5 years. SETTING: Tertiary and private care teaching hospital. PATIENTS: Between June 1993 and November 1995, 23 patients with stage N0 intermediate-thickness melanoma of the head and neck were enrolled in this volunteer sample. INTERVENTIONS: Twenty-four hours prior to surgery, a radioactive tracer was intradermally injected around the circumference of a primary melanoma. Twelve patients also had blue dye injected just prior to surgical resection. Using a handheld gamma probe, radiolabeled lymph nodes were identified and selectively removed with minimal dissection. In patients with nodes with histologic evidence of metastases, a regional lymphadenectomy was performed. MAIN OUTCOME MEASURES: The successful identification of radiolabeled SLNs, the correlation of SLN radiolabeling to lymphoscintigraphy and blue-dye mapping, and the long-term development of regional metastases. RESULTS: Surgeons successfully resected the radiolabeled SLNs in 22 (96%) of 23 patients. The success rate of blue-dye lymphatic mapping was 8 (75%) of 12 patients and lymphoscintigraphy was 20 (91%) of 22 patients. One hundred percent of blue-stained lymph nodes were radiolabeled. The one patient in whom no SLN could be identified developed regional disease at 17 months. CONCLUSIONS: Gamma-probe radiolocalization and resection of the radiolabeled SLN is a simple and reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

Adult↗
PubMed1998

Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical analysis of seven cases.

Merkel cell carcinoma (MCC) is a rare cutaneous skin lesion with a variable but often aggressive clinical course. Patient survival correlates with nodal status and the presence of distant metastases. The histologic status of the sentinel lymph node consistently correlates with the incidence of regional lymphatic metastases in other dermal malignancies. The technique of radiolocalization and surgical resection of the sentinel lymph node using an intraoperative gamma probe is used to guide clinical management in these patients. We report on seven cases of MCC managed utilizing this technique. Four patients had negative sentinel nodes and no other nodal disease at completion lymphadenectomy (n = 2) or clinical follow-up (n = 2) and currently remain disease free. Two patients had a positive sentinel node but no other positive lymph nodes at completion lymphadenectomy; one of them developed regional recurrence. One patient with a positive sentinel node and six additional positive nodes developed extensive nodal disease and systemic recurrence during radiotherapy and expired of MCC. Our results suggest that the sentinel node was identified and removed successfully using radiolocalization making this technique useful in the staging and therapy of patients with MCC.

Aged↗