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Biomedical subjects

N M Hansen

Publications and source records attributed to N M Hansen.

At least 19 recordsLinked to original sources

Surgical management of breast cancer in the elderly patient.

BACKGROUND: Breast cancer in the older woman is a major health issue and therapeutic challenge. This study asked if presentation, surgical treatment, and outcome of breast cancer are different in elderly women compared with their younger counterparts. METHODS: There were 816 women < 70 years (younger) and 190 > or = 70 years (older) treated surgically for breast carcinoma between January 1992 and April 2000. Data for younger and older patients was analyzed from our prospective database. RESULTS: More older women had mammographic lesions (P < 0.006). Breast conservation was the treatment of choice for both groups. Stage, tumor size, histology and disease-specific survival were similar for both. There was no evidence of disease in 93% of cases in the < 70 years group at median follow-up of 38.4 months and 91% for the > or = 70 years group at 44.5 months. CONCLUSIONS: In our population the presentation, surgical treatment, and survival from breast cancer is similar in older and younger women.

Adult↗

Microsatellite alterations detected in the serum of early stage breast cancer patients.

Breast cancer is the most common malignancy affecting women. Advances in screening have resulted in an increasing trend towards detecting earlier stage tumors associated with a longer disease-free survival. Because of this prolonged latency period, it is critical to identify patients early in their disease course who are at increased risk for recurrence, whereby treatment decisions may be altered accordingly based on more precise information. Molecular markers that demonstrate prognostic importance as well as utility for assessing subclinical disease progression offer one such approach. Specifically, circulating microsatellite alterations that reflect those genetic events occurring in tumors and that can be serially assessed through a minimally invasive procedure are a logistically practical method. In this study, serum was collected preoperatively from 56 patients with early stage breast cancer (AJCC stages I/II) and assessed for loss of heterozygosity (LOH) using 8 microsatellite markers. Twelve (21%) of 56 patients demonstrated LOH in their serum for at least one marker. Histopathologic correlation revealed an association between the presence of circulating LOH in serum and those tumors with increased proliferation indices as characterized by an increased diploid index, elevated MIB-1 fraction, and abnormal ploidy. These findings demonstrate the presence of circulating microsatellite alterations in the serum from patients with early stage breast cancer. The association of known poor prognostic features found in tumors with increased nuclear activity not only suggests a possible etiology for their presence, but also offers a potential blood-based surrogate marker for this disease that may demonstrate clinical utility in long-term follow-up studies.

Breast Neoplasms↗

Blue versus hot: learning the techniques with dye and isotopes.

Intraoperative lymphatic mapping and sentinel node (SN) biopsy has generated a tremendous amount of interest in the field of surgical oncology since its introduction for patients with early-stage melanoma. The SN concept has been applied recently to many solid tumors, including melanoma, breast cancer, thyroid cancer, gynecological malignancies, and colorectal cancers. Although the concept of intraoperative lymphatic mapping and SN biopsy has been validated in multiple single-institution studies as well as multicenter trials, there is still much discussion as to which mapping technique is easier to learn. This article focuses on the technical aspects of SN mapping in breast cancer and reviews the most recent data to try to determine which technique is superior.

Breast Neoplasms↗

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

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

Adult↗

Does sentinel lymphadenectomy improve staging and alter therapy in elderly women with breast cancer?

BACKGROUND: Routine axillary lymph node dissection (ALND) for elderly women with invasive breast cancer has been questioned because it rarely alters therapy yet carries a significant morbidity rate. Sentinel lymphadenectomy (SLND) improves axillary staging and alters therapy in women with T1 breast cancer, but it is not clear whether SLND alters therapy in elderly women with breast cancer. METHODS: A prospective breast cancer data base was used to identify women 70 years old and older who underwent SLND for axillary staging of invasive breast cancer between 1991 and 1998. RESULTS: There were 75 invasive breast cancers in 73 women. The mean patient age was 74.5 years (range, 70-90 years). Median tumor size was 1.4 cm (range, 0.1-6.2 cm). Of the 75 tumors, 42 (56%) had favorable primary characteristics; the remaining tumors had unfavorable characteristics. SLND was performed alone in 17 cases (23%) and was followed by completion ALND in 58 cases (77%). Positive lymph nodes were identified in 32 cases (43%); 26 (81.3%) were detected by hematoxylin and eosin stains, and 6 (18.7%) were detected by immunohistochemistry alone. Five patients (6.9%) received adjuvant chemotherapy. Seven patients (9.6%) received axillary/supraclavicular radiation for positive nodes. Ten (13.7%) of 73 patients had obvious alterations in therapy because of axillary nodal status. As a result of SLND, 3 (13.6%) of 22 patients with tumors 1.0 cm or smaller received tamoxifen, and 7 (15%) of 46 patients with tumors between 1.0 and 3.0 cm in size had changes in therapy. When patient and tumor characteristics were analyzed to determine relationships to therapeutic decision-making, nodal status was the variable most significantly associated with changes in therapy (P = .0001). CONCLUSIONS: SLND improves axillary staging in elderly women with invasive breast cancer. Results of immunohistochemistry do not alter therapy in this group of individuals (P = .6367). In patients with small primary tumors, SLND alters therapy by increasing the number of patients receiving tamoxifen. In addition, SLND affects adjuvant systemic chemotherapy and regional radiotherapy in a significant number of patients with larger tumors, particularly tumors between 1.0 and 3.0 cm.

Aged↗

Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer.

PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically </= 4 cm in diameter and no axillary lymphadenopathy were prospectively entered onto a trial of SLND using vital blue dye. Sentinel nodes were examined by standard microscopy or immunohistochemistry. SLND was the only axillary surgery if sentinel nodes were tumor-free. Completion ALND was performed only if sentinel nodes contained metastases or if they were not identified. Excluded from subsequent analysis were patients with unsuspected multifocal carcinoma and those who refused completion ALND. The complication and axillary recurrence rates after SLND without ALND were determined. RESULTS: Sentinel nodes were identified in 132 (99%) of 133 patients. Eight patients were excluded from further analysis. Of the 125 assessable patients, 57 had tumor-positive sentinel nodes and one had an unsuccessful mapping procedure; these patients underwent completion ALND. In the remaining 67 patients (54%), SLND was the only axillary procedure. Complications occurred in 20 patients (35%) undergoing ALND after SLND but in only two patients (3%) undergoing SLND alone (P =.001). There were no local or axillary recurrences at a median follow-up of 39 months. CONCLUSION: Complication rates are negligible after SLND alone. An absence of axillary recurrences supports SLND as an accurate staging alternative for breast cancer and suggests that routine ALND can be eliminated for patients with histopathologically negative sentinel nodes.

Adult↗

Factors affecting sentinel node localization during preoperative breast lymphoscintigraphy.

UNLABELLED: Variable success rates for identifying axillary (AX) sentinel nodes in breast cancer patients using preoperative lymphoscintigraphy have been reported. We evaluated the effects of age, weight, breast size, method of biopsy, interval after biopsy, and imaging view on the success of sentinel node identification and on the kinetics of radiopharmaceutical migration. METHODS: Preoperative breast lymphoscintigraphy was performed in consecutive breast cancer patients from February 1998 to December 1998. The ipsilateral shoulder was elevated on a foam wedge and the arm was abducted and elevated overhead. Imaging using this modified oblique view of the axilla (MOVA) started immediately after peritumoral injection of Millipore-filtered 99mTc-sulfur colloid and continued until AX sentinel nodes were identified. Anterior views were obtained after MOVA. AX, internal mammary (IM), and clavicular (CL) basins were monitored in all patients. MOVA was compared with the anterior view for sentinel node identification. Age, weight, breast size, method of biopsy, interval after biopsy, and primary tumor location were evaluated for their effects on sentinel node localization and transit times from injection to arrival at the sentinel nodes. RESULTS: Seventy-six lymphoscintigrams were obtained for 75 patients. AX sentinel nodes were revealed in 75 (99%) cases. IM or CL sentinel nodes were found in 19 (25%) cases and were not related to tumor location; exclusive IM drainage was present in 1 (1%) case. Identification of AX sentinel nodes was equivalent with MOVA and anterior views in 18 (24%) patients, was better with MOVA in 20 (26%) patients, and was accomplished only with MOVA in 38 (50%) patients. Median transit time was 17.5 min (range, 1 min to 18 h) after injection, and larger breast size was associated with increased transit time. No effect of age, weight, biopsy method, interval from biopsy, or tumor location on transit time was found. CONCLUSION: Use of MOVA can improve identification of AX sentinel nodes. Although AX drainage is the predominant pattern, a tumor in any portion of the breast can drain to IM sentinel nodes. Transit time was influenced by breast size. Overall short arrival times with this technique allow sentinel lymph node dissection to be performed on the same day as lymphoscintigraphy.

Axilla↗

Sentinel node metastasis in patients with breast carcinoma accurately predicts immunohistochemically detectable nonsentinel node metastasis.

BACKGROUND: Sentinel lymphadenectomy is highly accurate for identifying axillary metastasis from a primary breast carcinoma. Nonsentinel axillary lymph nodes (NSNs) are unlikely to contain tumor cells if the axillary sentinel node (SN) is tumor free. We previously showed that the size of the primary tumor and the size of its SN metastasis predict the risk of NSN tumor involvement detected by hematoxylin and eosin staining. This study used immunohistochemical staining (IHC) to determine the likelihood of NSN axillary metastasis in the presence of SN metastasis. METHODS: Between 1991 and 1997, axillary lymphadenectomy was performed in 156 women (157 axillary basins) who had primary breast carcinoma with SN metastasis. By hematoxylin and eosin staining, we identified NSN metastasis in 55 axillae (35%). IHC was then used to re-examine all NSNs (1827 lymph nodes) from the remaining 102 axillae. The incidence of IHC-detected NSN involvement was analyzed with respect to clinical and tumor characteristics. RESULTS: By using IHC, we identified NSN metastasis in 15 (14.7%) of the 102 axillae. By multivariate analysis, the size of the SN metastasis (P = .0001) and the size of the primary tumor (P = .038) were the only independent variables predicting NSN metastasis determined by using either hematoxylin and eosin staining or IHC. Only the number of SN metastases (1 vs. >1) was a significant (P = .04) predictor of IHC-detected NSN metastasis. CONCLUSIONS: Use of IHC increases the likelihood of detection of NSN metastasis, and the risk of IHC-detected metastasis increases with the size of the SN metastasis and the size of the primary tumor. If SN involvement is micrometastatic (< or =2 mm) or detected by using IHC, tumor cells are unlikely to be found in other axillary lymph nodes in patients with a small primary tumor. The clinical significance of micrometastatic disease in lymph nodes is controversial, and a prospective randomized study is necessary to resolve this important issue.

Adult↗

Intraoperative examination of the sentinel lymph node for breast carcinoma staging.

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Adenocarcinoma↗

Do all patients with sentinel node metastasis from breast carcinoma need complete axillary node dissection?

OBJECTIVE: To determine the likelihood of nonsentinel axillary metastasis in the presence of sentinel node metastasis from a primary breast carcinoma. SUMMARY BACKGROUND DATA: Sentinel lymphadenectomy is a highly accurate technique for identifying axillary metastasis from a primary breast carcinoma. Our group has shown that nonsentinel axillary lymph nodes are unlikely to contain tumor cells if the axillary sentinel node is tumor-free, but as yet no study has examined the risk of nonsentinel nodal involvement when the sentinel node contains tumor cells. METHODS: Between 1991 and 1997, axillary lymphadenectomy was performed in 157 women with a tumor-involved sentinel node. Fifty-three axillae (33.5%) had at least one tumor-involved nonsentinel node. The authors analyzed the incidence of nonsentinel node involvement according to clinical and tumor characteristics. RESULTS: Only two variables had a significant impact on the likelihood of nonsentinel node metastasis: the size of the sentinel node metastasis and the size of the primary tumor. The rate of nonsentinel node involvement was 7% when the sentinel node had a micrometastasis (< or =2 mm), compared with 55% when the sentinel node had a macrometastasis (>2 mm). In addition, the rate of nonsentinel node tumor involvement increased with the size of the primary tumor. CONCLUSIONS: If a primary breast tumor is small and if sentinel node involvement is micrometastatic, then tumor cells are unlikely to be found in other axillary lymph nodes. This suggests that axillary lymph node dissection may not be necessary in patients with sentinel node micrometastases from T1/T2 lesions, or in patients with sentinel node metastases from T1a lesions.

Adult↗

Urokinase plasminogen activator is necessary but not sufficient for prostate cancer cell invasion.

The expression and function of urokinase plasminogen activator (uPA), an extracellular protease, were examined in four established prostate cancer lines, and one uPA-transfected cell line. The cell lines exhibited variable efficiency in uPA transcription, translation and specific proteolytic activity. A statistically significant inhibition of Boyden chamber invasion by anti-uPA monoclonal antibodies was demonstrated in cell lines TSU-PR1 and PC3. This inhibition suggests a direct role for uPA in the invasion of prostate cancer. However, variable processing of uPA mRNA, protein and proteolytic activity make prediction of in vitro invasion of prostate cancer difficult. Stable transfection experiments suggest that the proteolytic cascade generated by a cell is multiform and solitary alterations in uPA may not modify the proteolytic capability for invasion.

Animals↗

The biplane frame: modified compression arthrodesis of the knee.

For many years knee arthrodesis has been recommended for patients with severe degenerative disease complicated by obesity, venous insufficiency or old sepsis. Recently, failed total knee arthroplasties are being treated by arthrodesis, but these new indications entail new and difficult circumstances. A biplane fixation frame, more rigid than the Charnley clamp, and the instrumentation for producing absolutely flat opposing surfaces are important. The frame provides the advantages of good access to the wound and permits early ambulation. Pin tract loosening and infection are potential disadvantages, but in this small series were not significant.

Arthrodesis↗

Aggregation of calcium oxalate crystals: effect of urine and various inhibitors.

The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.

Calcium↗

Aggregation of hydroxyapatite crystals.

A system to study the aggregation of hydroxyapatite crystals was developed. The effect of several factors (Ca2+ x Pi product, Ca2+/Pi ratio, pH, and various substances) were tested. Pb2+, Zn2+, Mg2+ and methyleneblue had only small effects; citrate inhibited aggregation. Pyrophosphate was a strong inhibitor and the diphosphonates disodium ethane-1-hydroxy-1,1-diphosphonate and disodium dichloromethylene diphosphonate were even more potent. The monophosphonate pentanemonophosphonate had no effect. Potent inhibition also occurred with glycosaminoglycans: heparin greater than hyaluronic acid greater than dermatan sulfate greater than chondroitin 4-sulfate greater than chondroitin 6-sulfate. Urine also showed high inhibitory activity. The inhibition of heparin but not that of hyaluronic acid, PPi or urine was abolished by egg white lysozyme. The effects described might be relevant in the normal mineralization process as well as in the mechanisms leading to pathological calcification, such as urinary stone formation.

Binding Sites↗

Disaggregation of hydroxyapatite crystals.

A system has been developed to measure quantitatively the disaggregation of hydroxyapatite crystals. Disaggregation was induced by pyrophosphate, ethane-1-hydroxy-1,1-diphosphonate, dichloromethylene diphosphonate, haparin and citrate. Hyaluronic acid stimulated aggregation at low concentrations and disaggregation at high concentrations. Lactate had no effect. The possible role disaggregation might play in the resorption of calcified tissues in vivo id discussed.

Binding Sites↗