Sentinel node localization in patients with breast cancer

BACKGROUND: Intraoperative lymphatic mapping and identification of the first draining lymph node (the sentinel node) may allow some patients with breast cancer to avoid the morbidity of formal axillary clearance. The aim of this pilot study was to establish the reliability of the technique in predicting axillary node status. METHODS: Sixty-eight consecutive patients with breast cancer, 38 undergoing mastectomy and 30 wide local excision, were included. Some 2-4 ml of 2.5 per cent Patent Blue dye was injected into adjacent breast tissue on the axillary side of the primary tumour. After 5-10 min, the axilla was explored. Blue-stained lymphatics were dissected to the sentinel node, which was removed for frozen-section examination, followed by routine histology. Formal axillary dissection was then completed. RESULTS: A sentinel lymph node was identified successfully in 56 (82 per cent) of 68 patients. Histology of the sentinel node accurately predicted axillary node status in 53 (95 per cent). There were three false negatives (5 per cent). In each case, only a single non-sentinel node was tumour positive. Sensitivity and specificity were 83 and 100 per cent respectively. CONCLUSION: This technique would allow a selective policy of formal axillary dissection in only node-positive patients; however, further experience and refinement are needed.     

Sentinel lymph node biopsy for staging breast cancer

Cadherin-11 is a calcium-dependent cell adhesion molecule that is expressed in cells of the mesenchymal lineage during embryonic development. In this study we show, for the first time, that cadherin-11 gene is expressed in the bone marrow and bone cells obtained from rabbits of various age groups. Furthermore, a quantitative measurement of gene expression revealed that cadherin-11 was expressed in young rabbits (6 week-old: open epiphysis) at a level of 6.7 x 10(5) +/- 0.7 x 10(5) molecules; in mature rabbits (8-10 month-old: closed epiphysis) at 11 x 10(5) +/- 0.9 x 10(5) molecules; and in aged rabbits (4-5 year-old) at a level of 1.2 x 10(5) +/- 0.2 x 10(5) molecules/microg total RNA. The relative level of cadherin-11 gene expression in mature rabbit marrow was found to be approximately 50% greater than in young rabbits. However, aged animals showed a reduction in cadherin-11 specific gene expression of greater than 900% as compared with mature animals. Age-related changes in bone remodeling/turnover lead to reduced bone density and high fracture risk, and since cadherins play a crucial role in tissue morphogenesis, this marked decrease may represent an index of the aging process in bone.     

Sentinel node detection in breast carcinoma

The aim of sentinel node biopsy (SN) in breast cancer patients is to detect the tumor-draining lymph node by means of isosulfan blue or 99mTc-labelled colloids. SN can be detected in 80 to 85% of the patients, depending on the size of the tumor. Preoperative lymphoscintigraphy permits the draining nodes along the internal mammary artery also to be visualized. The predictive value of the histological findings of SN for lymph nodes obtained from axillary dissection is about 95%. Because of different diagnostic procedures using various radiotracers each center has to follow its own learning curve. To be sure that the nodal status derived from a SN procedure is of identical value to axillary dissection about 100 patients have to undergo sentinel node detection, followed by axillary dissection, and concordant results should be obtained in 95% of them at least. The SN, however, offers a chance of assessing the lymph node at risk for metastasis by more detailed histological procedures. Morbidity as a result of treatment for primary breast cancer can be decreased if only patients suffering from metastatic disease are subjected to axillary dissection. Currently, the indication criteria for a SN procedure should be restricted to small tumors (T1) with clinically uninvolved axillary status and patients with ductal carcinoma in situ (DCIS).     

Sentinel lymph node biopsy for melanoma

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.     

Lymphatic mapping and sentinel node biopsy in breast cancer

BACKGROUND: Sentinel lymph node biopsy is a recently developed, minimally invasive technique for staging the axilla in patients with breast cancer. It has been suggested that this technique will avoid the morbidity associated with more extensive axillary dissection. A wide range of different methods and materials has been employed for lymphatic mapping, but there has been little consensus on the most reliable and reproducible technique. METHODS: This is a comprehensive review of all published literature on sentinel node biopsy in breast cancer, using the Medline and Embase databases and cross-referencing of major articles on the subject. RESULTS AND CONCLUSION: Sentinel node biopsy is a valid technique in breast cancer management, providing valuable axillary staging information. The optimal technique of lymphatic mapping utilizes a combination of vital blue dye and radiolabelled colloid. However, there remain controversial issues which require to be resolved before sentinel node biopsy becomes a widely accepted part of breast cancer care.     

Axillary lymph node microcalcifications disclosing breast cancer]

It is well known that vertebral schisis is frequent in enuretic children but the true incidence in the normal population is not clear, because all series published are referred to children with associated urinary anomalies, who were submitted to voiding cystography and or intravenous pyelography. This determine a statistical bias. The aim of our study was to compare the prevalence of vertebral schisis in enuretic children and in the general pediatric population. Therefore, we chose 142 enuretic children without associated urological or neurological anomalies and a control group of 152 children, assumed as general population, who were submitted to spinal X-rays during screening for scoliosis or congenital dysplasia of the hip. Vertebral schisis was found in 65% (93/142) of enuretics and in 18% (28/152) of control group children. Maximum association between enuresis and vertebral schisis was found in primary monosymptomatic nocturnal enuresis (82%), while minimum association was found in children with secondary enuresis (57%). The difference in percentage of association enuresis-schisis was statistically significant between enuretics and control group and between primary monosymptomatic and secondary enuresis (p < 0.001). The results of this paper are simply add knowledges on the prevalence of the sacral schisis in enuretic children. But, to speculate the different prevalence in different types of enuresis, the results should confirm that the phenomenon of enuresis is multifactorial and the primary monosymptomatic and secondary enuresis have different etiological factor.     

Aromatase expression and its localization in human breast cancer

Aromatization or in situ estrogen production by aromatase has been considered to play an important role in the development of human breast carcinoma. In the human breast, aromatase overexpression is observed in the stromal or interstitial cells of the carcinoma, especially at the sites of frank invasion and/or adipose tissue. Transplantation experiments in the nude mouse employing MCF-7 and/or SF-TY human fibroblast cell lines revealed that aromatase activity and expression were much higher in the tumour with MCF-7 and SF-TY than that with MCF-7 alone. Aromatase overexpression in human breast carcinoma tissue is considered to occur as a result of carcinoma-stromal cell interactions, i.e. paracrine communication between stromal and carcinoma cells. Aromatase overexpression is correlated with the malignant phenotype in the human breast, but not with stage, age, clinical stages, clinical course, or proliferative activity of breast carcinoma. Aromatase overexpression may be correlated with development, rather than the biological behaviour of breast malignancy. Aromatase overexpression is not necessarily correlated with expression of 17beta-hydroxysteroid dehydrogenase type 1, which converts estrone to estradiol and estrogen receptor. Different mechanisms may be involved in the regulation of expression of these two important estrogen-metabolizing enzymes and estrogen receptor in human breast cancer. Aromatase overexpression in intratumoral stromal cells was much more frequently detected in male breast cancer than in female counterparts, which confers a growth advantage on cancer cells in a male hormonal environment with low serum estrogen levels.     

Identification of sentinel and axillary node involvement in breast cancer

Axillary node dissection for breast cancer is important for staging and prognosis. "Sentinel nodes" are the first nodes into which primary cancer drains. Identification, removal and pathological examination of those nodes indicates whether completion of axillary lymphadenectomy is required. The sentinel nodes are identified using a vital dye injected at the primary tumor site. With this technique we were able to identify sentinel nodes in 46 of 48 (95%) women examined. An average of 2.7 +/- 1.2 nodes were identified as sentinel nodes. In 81% of cases there was a correlation between involvement of sentinel nodes and of other axillary nodes as well. In 10% of patients sentinel nodes were involved with tumor while other axillary nodes were negative. The major problem in routine application of this is relationship in surgical decisions is reliable real time pathological identification of lymph node involvement by tumor.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Treatment of breast cancer with ipsilateral supraclavicular node metastases

During 1954-1977, among 2803 cases of breast cancer 99 (3.5%) had ipsilateral supraclavicular node mestastases. The results of treatment are reported, based on follow-up for more than 10 years. According to the treatment modality, the patients were divided into 4 groups: I. surgery with postoperative adjuvant chemotherapy and radiation therapy; II. radiation and chemotherapy; III. chemotherapy; IV. no treatment. In group I, surgical procedures consisted of segmental mastectomy in 6; simple mastectomy in 7; modified radical mastectomy in 16; standard radical mastectomy in 12, and extended radical mastectomy in 3. The over-all five-year survival rate was 9%. It was 18% (8/44) in group I, but only 5% (1/21) in group II. None survived for 5 years in group III and group IV. The results seem to indicate that more aggressive multi-modality treatment of breast cancer with ipsilateral supraclavicular lymph node metastases is indicated to expect better survival.     

The sentinel node biopsy in patients with breast cancer: recommendations for the introduction of this procedure. Dutch Working Group Sentinel Node Biopsy in Breast Cancer

Sentinel node biopsy may be useful in the staging of breast cancer. In experienced hands presence or absence of metastasis in the sentinel node accurately predicts the nodal status and in patients with a negative sentinel node biopsy axillary dissection may be avoided. The technique, however, shows a clear learning curve and hasty introduction may lead to an unacceptable rate of false negative biopsies. Moreover, the introduction of the technique in general practice should be well coordinated in order to prevent large differences between hospitals in the staging and treatment of breast cancer patients. On the initiative of NABON (Nationaal Borstkanker Overleg Nederland; 'national breast cancer consultation') and the Nederlandse Vereniging voor Chirurgische Oncologie (Netherlands Association for Surgical Oncology) a study group was formed to co-ordinate the introduction of the sentinel node biopsy in breast cancer patients in the Netherlands. Important topics are central registration of all procedures in order to evaluate its applicability and technical variations, the performance in each centre of at least 50 procedures together with axillary node dissection to evaluate the results before clinical application is considered, and nationwide co-ordination to find the best therapy for patients with positive sentinel nodes.     

Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer

Lymphoscintigraphy associated with radioguided biopsy of the sentinel node (SN) is well established in clinical practice for melanoma. In breast cancer, the SN concept is similarly valid, and lymphoscintigraphy is a useful method for localizing the axillary SN. The aim of this study was to optimize the lymphoscintigraphy technique in association with a gamma ray detecting probe (GDP) for identifying and removing the SN in breast cancer patients. METHODS: Two-hundred fifty patients with operable breast tumor underwent lymphoscintigraphy before surgery. Three different size ranges of 99mTc-labeled colloid particles (<50, <80 and 200-1000 nm) were used, with either subdermal (above tumor) or peritumoral injection. Early and late scintigraphic images were obtained in anterior and oblique projections, and the skin projection of the detected SN was marked. Sentinel nodes were identified and removed with the aid of the GDP during breast surgery; they were tagged separately. Complete axillary dissection followed. In 40 patients, a blue dye was also administered in addition to subdermal radiolabeled colloid to compare blue dye mapping with lymphoscintigraphy localization. RESULTS: Lymphoscintigraphy successfully revealed lymphatic drainage in 245 of 250 patients (98%). The axillary SN was identified in 240 patients (96%). SN biopsy correctly predicted axillary node status in 234 of 240 patients (97.5%). Lymphoscintigraphy and GDP detected the SN most easily and consistently when 200-1000 nm colloid was administered subdermally in an injection volume of 0.4 ml. Blue dye mapping was successful in 30 of 40 patients (75%). In 26 of these patients, the dye and lymphoscintigraphy identified the same node; in 4 cases different nodes were identified. None of these four patients had axillary disease. CONCLUSION: Lymphoscintigraphy is a simple procedure that is well tolerated by patients. Sentinel node identification is more reliable when large-size radiolabeled colloids are injected in a relatively small injection volume (0.4 ml). Use of a GDP greatly facilitates precise pinpointing and rapid removal of the SN.     

Demonstration of the sentinel lymph node in axillary dissection for breast cancer

OBJECTIVES: The sentinel node is defined as the first-line axillary lymphatic drainage node in breast cancer. If the sentinel node can be identified, during axillary dissection for breast cancer, resection could be limited reducing subsequent morbidity. However, before modifying the standard dissection procedure, it is important to prove that the sentinel node is representative of the metastatic status of other axillary nodes. PATIENTS AND METHODS: Between March and December 1996, 86 patients (mean age 58 years, range 32-82) underwent amputation (n = 20), tumorectomy with dissection (n = 56) or tumorectomy followed by secondary dissection (n = 10) for breast cancer. Ten ml of diluted patent blue was injected either into the peripheral portion of the tumor or the tumorectomy cavity. Node dissection was performed 10 to 20 minutes after injection. The blue sentinel node was identified prior to standard dissection. RESULTS: A mean 12 nodes were removed (range 4-21). Seventy-nine sentinel nodes were identified (91%) and in 7 cases (8%) a sentinel node could not be identified. In 7 other cases the sentinel node was a false negative, i.e. non malignant despite metastases in other dissected nodes. In all the other cases, the status of the sentinel node predicted the status of the other nodes, i.e. a non-metastatic sentinel node associated with other metastatic nodes. Finally, in 7 cases, the sentinel node was the only invaded node among the nodes dissected. During the last 3 months of the study, the sentinel node was identified in 100% of the cases and was representative of the overall dissection. CONCLUSION: Identifying the sentinel node is an alternative to standard axillary node dissection procedures. The method requires a training period and identification can be improved with radioimmunologic guidance. Patient selection within the framework of a rigorous multidisciplinary protocol is indispensable. A nationwide study is currently being conducted to validate these preliminary results.